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1.
Inácio, Ana Filipa Ferreira da Costa Palma.
A terapêutica com o omeprazol: avaliação da potencial relação com a suscetibilidade ao cancro.
Degree: 2012, RCAAP
URL: http://www.rcaap.pt/detail.jsp?id=oai:sapientia.ualg.pt:10400.1/3016 
► Dissertação de mest., Ciências Farmacêuticas, Faculdade de Ciências e Tecnologia, Univ. do Algarve, 2012
O omeprazol, principal benzimidazol substituído utilizado na inibição da secreção gástrica,…
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▼ Dissertação de mest., Ciências Farmacêuticas, Faculdade de Ciências e Tecnologia, Univ. do Algarve, 2012
O omeprazol, principal benzimidazol substituído utilizado na inibição da secreção gástrica, através do bloqueio da ATPase da célula parietal, é um dos 10 fármacos mais prescritos do mundo. Farmacodinamicamente aliciante, dada a sua extraordinária seletividade química, o omeprazol foi um sucesso imediato, desde o seu lançamento, em 1988. Para além da sua eficácia altamente satisfatória, o omeprazol é, à semelhança, um fármaco farmacocineticamente ideal, uma vez que desfruta de um tempo de meia-vida curto, e concentra-se e é ativado no seu local de ação, onde exibe uma longa duração terapêutica. É considerado um fármaco seguro e não apresenta eventos secundários marcados, nem efeitos a longo prazo, conhecidos, significativos.
A metabolização do omeprazol é da responsabilidade do sistema de Citocromos P450, mais concretamente dos CYP2C19 e CYP3A4. Ambos os enzimas são regulados pelos xenosensores celulares PXR e CAR, os quais estão envolvidos em processos que conduzem à variabilidade da metabolização e excreção do omeprazol.
O omeprazol é indutor dos CYP1A, através de um mecanismo indutor diferente do adotado pela maioria dos agonistas do recetor AhR, responsável pela regulação destes enzimas. A indução dos CYP1A1 e CYP1A2, pelo omeprazol, é efetuada por um processo misto, que consiste na ligação direta, do fármaco, a um local secundário do AhR, que não o sítio ativo e, adicionalmente, através da ativação indireta do recetor, por estimulação da fosforilação do mesmo, mediada por proteínas tirosina cinases.
Os CYP1A estão envolvidos na ativação metabólica de substratos policíclicos e aromáticos, presentes no fumo do tabaco e carnes cozinhadas, em metabolitos eletrofílicos e instáveis, que se ligam covalentemente ao ADN e outras moléculas endógenas, com consequente possibilidade de evolução para um quadro tumoral.
Dado a capacidade do omeprazol estimular enzimas envolvidos na geração de substâncias tóxicas e reativas, questionou-se a possibilidade de a terapêutica com o fármaco adicionar risco na suscetibilidade ao cancro. Até à data, estas especulações têm se provado infundadas e após mais de 20 anos de uso clínico, o omeprazol continua a ser um fármaco seguro e prescrito a milhões doentes, todos os anos.
Advisors/Committee Members: Ribeiro, Vera.
Subjects/Keywords: Omeprazol; AhR; Indução enzimática; CYP1A1; CYP1A2; Cancro
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APA (6th Edition):
Inácio, A. F. F. d. C. P. (2012). A terapêutica com o omeprazol: avaliação da potencial relação com a suscetibilidade ao cancro. (Thesis). RCAAP. Retrieved from http://www.rcaap.pt/detail.jsp?id=oai:sapientia.ualg.pt:10400.1/3016
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Inácio, Ana Filipa Ferreira da Costa Palma. “A terapêutica com o omeprazol: avaliação da potencial relação com a suscetibilidade ao cancro.” 2012. Thesis, RCAAP. Accessed April 17, 2021.
http://www.rcaap.pt/detail.jsp?id=oai:sapientia.ualg.pt:10400.1/3016.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Inácio, Ana Filipa Ferreira da Costa Palma. “A terapêutica com o omeprazol: avaliação da potencial relação com a suscetibilidade ao cancro.” 2012. Web. 17 Apr 2021.
Vancouver:
Inácio AFFdCP. A terapêutica com o omeprazol: avaliação da potencial relação com a suscetibilidade ao cancro. [Internet] [Thesis]. RCAAP; 2012. [cited 2021 Apr 17].
Available from: http://www.rcaap.pt/detail.jsp?id=oai:sapientia.ualg.pt:10400.1/3016.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Inácio AFFdCP. A terapêutica com o omeprazol: avaliação da potencial relação com a suscetibilidade ao cancro. [Thesis]. RCAAP; 2012. Available from: http://www.rcaap.pt/detail.jsp?id=oai:sapientia.ualg.pt:10400.1/3016
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
2.
Spyrou, Ioannis.
Μελέτη των επιπέδων έκφρασης των κυτοχρωμάτων P450 CYP1A1 και CYP1B1 σε ιστούς από καρκίνο του παχέος εντέρου.
Degree: 2016, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)
URL: http://hdl.handle.net/10442/hedi/38070
► The cytochrome P450 CYP1A1 and CYP1B1 enzymes are involved in carcinogenesis via activation of pro-carcinogenic compounds to carcinogenic metabolites. CYP1A1 and CYP1B1 have shown elevated…
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▼ The cytochrome P450 CYP1A1 and CYP1B1 enzymes are involved in carcinogenesis via activation of pro-carcinogenic compounds to carcinogenic metabolites. CYP1A1 and CYP1B1 have shown elevated levels in human tumors as determined by qRT-PCR and immunohistochemical studies. However studies that have examined CYP1 expression by enzyme activity assays are limited. In the current study the expression of CYP1A1 and CYP1B1 was investigated in a panel of human tumors of colorectal origin by qRT-PCR and enzyme activity assays. The results demonstrated that 35% (7/20) of colon tumors overexpressed active CYP1 enzymes. CYP1B1 mRNA was overexpressed 60% of colon tumors, whereas CYP1A1 was overexpressed in 80% of colon tumors. Mean mRNA levels of CYP1B1 and CYP1A1 along with mean CYP1 activity were higher in colon tumors compared to normal tissues (p<0.05). Statistical analysis revealed CYP1 expression levels to be independent of TNM status. Moreover, incubation of tumor microsomal protein in 3 colon samples with a CYP1B1 specific antibody revealed a large reduction (71.8 ± 7.2 %) in catalytic activity, indicating that the activity was mainly attributed to CYP1B1 expression. The study reveals active CYP1 overexpression in human tumors and uncovers the potential use of CYP1 enzymes and mainly CYP1B1 as targets for colorectal cancer therapy.
Τα κυτοχρώματα P450 CYP1A1 και CYP1B1 είναι ένζυμα που συμμετέχουν στην καρκινογένεση μέσω της ενεργοποίησης των προ-καρκινογόνων ενώσεων σε καρκινογόνους ενδιάμεσους μεταβολίτες. Τα CYP1A1 και CYP1B1 έχουν επιδείξει αυξημένη έκφραση σε ανθρώπινους όγκους μέσω ανίχνευσης με μεθόδους qRT-PCR και ανοσοϊστοχημείας. Ωστόσο οι μελέτες που έχουν εξετάσει την έκφραση των ανωτέρω κυτοχρωμάτων σε επίπεδο ενζυματικής δραστηριότητας είναι πολύ περιορισμένες. Στην παρούσα μελέτη η έκφραση των κυτοχρωμάτων CYP1A1 και CYP1B1 εξετάσθηκε σε μια σειρά όγκων από καρκίνο του παχέος εντέρου με μεθόδους qRT-PCR και ενζυματικής δραστηριότητας. Τα αποτελέσματα απέδειξαν ότι 35% (7/20) των όγκων είχαν αυξημένη έκφραση κυτοχρωμάτων P450 CYP1A1 και CYP1B1 σε επίπεδο ενζυματικής δραστηριότητας ενώ σε επίπεδο μεταγραφικής έκφρασης το CYP1A1 παρουσίασε υπερέκφραση σε ποσοστό 80% και το CYP1B1 σε ποσοστό 60%. Η μέση τιμή των επιπέδων μεταγραφής των CYP1A1 και CYP1B1 καθώς και η μέση τιμή των επιπέδων ενζυματικής δραστηριότητας ήταν αυξημένη σε δείγματα που προέρχονταν από καρκίνο του παχέος εντέρου σε σχέση με τα φυσιολογικά δείγματα (p < 0,05). Η στατιστική ανάλυση απέδειξε ότι τα επίπεδα έκφρασης των κυτοχρωμάτων ήταν ανεξάρτητα από το δείκτη νεοπλασματικής διήθησης. Επιπρόσθετα η επώαση 3 δειγμάτων από όγκο του παχέος εντέρου με ένα εξειδικευμένο CYP1B1 αντίσωμα απέδειξε μια μεγάλη μείωση στα επίπεδα ενεργότητας (71.8 ± 7.2%) η οποία ήταν ενδεικτική ενζυματικής δραστηριότητας του CYP1B1. Η μελέτη αποκαλύπτει για πρώτη φορά υπερέκφραση των κυτοχρωμάτων CYP1 σε επίπεδο ενζυματικής δραστηριότητας και εστιάζει στη χρήση των κυτοχρωμάτων CYP1 και κυρίως CYP1B1 στην αντικαρκινική θεραπεία.
Subjects/Keywords: Καρκίνος παχέος εντέρου; CYP1A1; CYP1B1; Colon tissue
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APA (6th Edition):
Spyrou, I. (2016). Μελέτη των επιπέδων έκφρασης των κυτοχρωμάτων P450 CYP1A1 και CYP1B1 σε ιστούς από καρκίνο του παχέος εντέρου. (Thesis). National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Retrieved from http://hdl.handle.net/10442/hedi/38070
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Spyrou, Ioannis. “Μελέτη των επιπέδων έκφρασης των κυτοχρωμάτων P450 CYP1A1 και CYP1B1 σε ιστούς από καρκίνο του παχέος εντέρου.” 2016. Thesis, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Accessed April 17, 2021.
http://hdl.handle.net/10442/hedi/38070.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Spyrou, Ioannis. “Μελέτη των επιπέδων έκφρασης των κυτοχρωμάτων P450 CYP1A1 και CYP1B1 σε ιστούς από καρκίνο του παχέος εντέρου.” 2016. Web. 17 Apr 2021.
Vancouver:
Spyrou I. Μελέτη των επιπέδων έκφρασης των κυτοχρωμάτων P450 CYP1A1 και CYP1B1 σε ιστούς από καρκίνο του παχέος εντέρου. [Internet] [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2016. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/10442/hedi/38070.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Spyrou I. Μελέτη των επιπέδων έκφρασης των κυτοχρωμάτων P450 CYP1A1 και CYP1B1 σε ιστούς από καρκίνο του παχέος εντέρου. [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2016. Available from: http://hdl.handle.net/10442/hedi/38070
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
3.
Suelene Ribeiro de Souza.
Análise do polimorfismo Mspl do gene CYP1A1m1 (Citocromo P450) em mulheres com endometriose.
Degree: 2012, Pontifícia Universidade Católica de Goiás
URL: http://tede.biblioteca.ucg.br/tde_busca/arquivo.php?codArquivo=1227
► Endometriose é uma enfermidade que afeta entre 10 e 15% das mulheres em idade reprodutiva. Caracterizada pela presença de tecidos semelhante a do endométrio, idênticos…
(more)
▼ Endometriose é uma enfermidade que afeta entre 10 e 15% das mulheres em idade reprodutiva. Caracterizada pela presença de tecidos semelhante a do endométrio, idênticos aos da cavidade uterina fora do útero. Apesar de algumas definições especificarem que o tecido ectópico funcional é sensível à ação de hormônios e seus mecanismos etiopatogênicos provavelmente envolvem anomalias imunológicas. O grau do comprometimento da endometriose é baseado no sistema proposto pela American Society for Reproductive Medicine (1985), com base nos achados de laparoscopia. Observa-se nos últimos 10 anos a crescente tendência em se utilizar um conjunto de marcadores para detectar alterações induzidas por xenobióticos. Inúmeros polimorfismos genéticos têm sido citados para o gene CYP1A1. O gene codifica enzimas da fase I envolvidas na desintoxicação no metabolismo de xenobióticos, codifica uma isoenzima que catalisa a oxidação de hidrocarbonetos aromáticos policíclicos (PAHs) em produtos fenólicos e epóxidos. Mapeado no e localizado no braço longo do cromossomo 15 (15q22-24). O objetivo do estudo foi analisar freqüência o polimorfismo do gene Mspl CYP1A1m1 com a endometriose. Foram analisadas 52 amostras de sangue periférico de mulheres com endometriose comprovadas por laparoscopia (FÉRTILE) com idades 25 a 35 anos mulheres e 42 amostras de mulheres sem endometriose com idades 25 a 57 anos (grupo controle). A análise molecular por meio da técnica da PCR (polymerase chain reaction). Constatou-se uma associação estatisticamente significativa (P= 0, 039) entre a endometriose e o alelo polimórfico m1 nas mulheres com endometriose (32,70%) quando comparadas ao grupo controle 14,29%. Concluiu-se que o polimorfismo m1 correlaciona-se com a endometriose e que os polimorfismos W1/m1 e m1/m1 estão mais freqüentes nas pacientes com infertilidade e com quadro clínico mais severo da endometriose.
Endometriosis is a disease that affects between 10 and 15% of women of reproductive age. Characterized by the presence of tissue resembling the endometrium similar to the uterine cavity outside the uterus, although some definitions specify that the ectopic tissue functional and sensitive to the action of hormones and their etiopathogenic mechanisms probably involve immunological abnormalities. The degree of involvement of endometriosis is based on the system proposed by the American Society for Reproductive Medicine (1985), based on the findings of laparoscopy. It is observed in the last 10 years, an increasing tendency to use a set of markers to detect changes induced by xenobiotics. Several genetic polymorphisms have been cited for the CYP1A1 gene, indicating a lack of functional protein that can cause an increase or a decrease in metabolic activity. The CYP1A1 gene encode the phase I enzymes involved in detoxification of estrogen metabolism, encodes an isoenzyme that catalyzes the oxidation of polycyclic aromatic hydrocarbons (PAHs) in phenolic compounds and epoxides. Mapped and located on the long arm of chromosome 15 (15q22-24). The aim of this study…
Advisors/Committee Members: PAULO ROBERTO DE MELO REIS, Katia Karina Verolli de Oliveira Moura, Daniela de Melo e Silva.
Subjects/Keywords: Endometriose; Gene CYP1A1; Polimorfismo MspI; Infertilidade; GENETICA; Endometriosis; Gene CYP1A1, MspI Polymorphism; Infertility
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APA ·
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APA (6th Edition):
Souza, S. R. d. (2012). Análise do polimorfismo Mspl do gene CYP1A1m1 (Citocromo P450) em mulheres com endometriose. (Thesis). Pontifícia Universidade Católica de Goiás. Retrieved from http://tede.biblioteca.ucg.br/tde_busca/arquivo.php?codArquivo=1227
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Souza, Suelene Ribeiro de. “Análise do polimorfismo Mspl do gene CYP1A1m1 (Citocromo P450) em mulheres com endometriose.” 2012. Thesis, Pontifícia Universidade Católica de Goiás. Accessed April 17, 2021.
http://tede.biblioteca.ucg.br/tde_busca/arquivo.php?codArquivo=1227.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Souza, Suelene Ribeiro de. “Análise do polimorfismo Mspl do gene CYP1A1m1 (Citocromo P450) em mulheres com endometriose.” 2012. Web. 17 Apr 2021.
Vancouver:
Souza SRd. Análise do polimorfismo Mspl do gene CYP1A1m1 (Citocromo P450) em mulheres com endometriose. [Internet] [Thesis]. Pontifícia Universidade Católica de Goiás; 2012. [cited 2021 Apr 17].
Available from: http://tede.biblioteca.ucg.br/tde_busca/arquivo.php?codArquivo=1227.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Souza SRd. Análise do polimorfismo Mspl do gene CYP1A1m1 (Citocromo P450) em mulheres com endometriose. [Thesis]. Pontifícia Universidade Católica de Goiás; 2012. Available from: http://tede.biblioteca.ucg.br/tde_busca/arquivo.php?codArquivo=1227
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
4.
Rogério Fenile.
Avaliação da presença do polimorfismo Msp1 da CYP1A1 do citocromo P-450 em mulheres assintomáticas portadoras de cisto mamário.
Degree: 2010, Universidade Federal de São Paulo
URL: http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2611
► Objetivo: o objetivo do estudo foi verificar a prevalência da alteração fibrocística da mama, na sua forma cística, dentre as diversas faixas etárias da população…
(more)
▼ Objetivo: o objetivo do estudo foi verificar a prevalência da alteração fibrocística da mama, na sua forma cística, dentre as diversas faixas etárias da população feminina e correlacionar a doença cística com a presença do polimorfismo Msp1 da
CYP1A1 do citocromo P450 . Casuística e métodos: Estudo retrospectivo, caso-controle, desenvolvido entre março de 2005 a março de 2007. Submeteram-se a exame ultra-sonográfico, 204 mulheres, sendo divididas em dois grupos: 44 com doença cística mamária (casos) e 149 sem doenças mamárias (controles); 11 mulheres foram excluídas. Foi realizado estudo genético para a detecção do
CYP1A1 através de reação em cadeia da polimerase e utilizado o teste de Fisher e c2 para a análise estatística. Resultados: A doença cística mamária diagnosticada pelo ultra-som esteve presente em 22% da população estudada. Os cistos eram do tipo simples em 93%, múltiplos em 75% dos casos, e mediam 4-10 mm em 46%. A mama esquerda no quadrante súpero-lateral foi a localização mais freqüente. O perfil epidemiológico-clínico dessas mulheres foi: branca, faixa etária de 41-50 anos, ciclos menstruais regulares, multípara e com queixa de mastalgia. Na análise genética do
CYP1A1, observamos homozigoto selvagem numa freqüência de 68,2% no grupo casos e 66% no controle; heterozigotos 31,28% no grupo estudo e 26,8% no controle.Não houve aparecimento do homozigoto mutado no grupo casos surgindo como 7,2% no controle. Não houve diferença estatisticamente significante entre os grupos (p = 0,42). Conclusão: A prevalência e quase todo o perfil epidemiológico da doença cística mamária foram compatíveis com a literatura. Houve maior freqüência de heterozigotos mutados no grupo de casos, porém não de homozigotos.Não houve associação estatisticamente significante entre o polimorfismo da
CYP1A1 e a doença fibrocística mamária na sua forma cística.
Advisors/Committee Members: Ismael Dale Cotrim Guerreiro da Silva, Afonso Celso Pinto Nazário, Silvio Eduardo Duailibi, Sophie Françoise Mauricette Derchain, Cristina Valletta de Carvalho.
Subjects/Keywords: Doença fibrocística mamária; Cisto mamário; CYP1A1; Polimorfismo; GINECOLOGIA E OBSTETRICIA; Polymorphism; CYP1A1; Fibrocystic disease; Breast cyst
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APA ·
Chicago ·
MLA ·
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APA (6th Edition):
Fenile, R. (2010). Avaliação da presença do polimorfismo Msp1 da CYP1A1 do citocromo P-450 em mulheres assintomáticas portadoras de cisto mamário. (Thesis). Universidade Federal de São Paulo. Retrieved from http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2611
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Fenile, Rogério. “Avaliação da presença do polimorfismo Msp1 da CYP1A1 do citocromo P-450 em mulheres assintomáticas portadoras de cisto mamário.” 2010. Thesis, Universidade Federal de São Paulo. Accessed April 17, 2021.
http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2611.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Fenile, Rogério. “Avaliação da presença do polimorfismo Msp1 da CYP1A1 do citocromo P-450 em mulheres assintomáticas portadoras de cisto mamário.” 2010. Web. 17 Apr 2021.
Vancouver:
Fenile R. Avaliação da presença do polimorfismo Msp1 da CYP1A1 do citocromo P-450 em mulheres assintomáticas portadoras de cisto mamário. [Internet] [Thesis]. Universidade Federal de São Paulo; 2010. [cited 2021 Apr 17].
Available from: http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2611.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Fenile R. Avaliação da presença do polimorfismo Msp1 da CYP1A1 do citocromo P-450 em mulheres assintomáticas portadoras de cisto mamário. [Thesis]. Universidade Federal de São Paulo; 2010. Available from: http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=2611
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
5.
Souza, Suelene Ribeiro de.
Análise do polimorfismo Mspl do gene CYP1A1m1 (Citocromo P450) em mulheres com endometriose.
Degree: 2012, Pontifícia Universidade Católica de Goiás; Genética; PUC Goiás; BR; Ciências Humanas
URL: http://localhost:8080/tede/handle/tede/2352
► Made available in DSpace on 2016-08-10T10:38:35Z (GMT). No. of bitstreams: 1 Suelene Ribeiro de Souza.pdf: 13184565 bytes, checksum: 005b5afc9db66a26778e81d9edec24fa (MD5) Previous issue date: 2012-03-27
Endometriosis…
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▼ Made available in DSpace on 2016-08-10T10:38:35Z (GMT). No. of bitstreams: 1 Suelene Ribeiro de Souza.pdf: 13184565 bytes, checksum: 005b5afc9db66a26778e81d9edec24fa (MD5) Previous issue date: 2012-03-27
Endometriosis is a disease that affects between 10 and 15% of women of reproductive age. Characterized by the presence of tissue resembling the endometrium similar to the uterine cavity outside the uterus, although some definitions specify that the ectopic tissue functional and sensitive to the action of hormones and their etiopathogenic mechanisms probably involve immunological abnormalities. The degree of involvement of endometriosis is based on the system proposed by the American Society for Reproductive Medicine (1985), based on the findings of laparoscopy. It is observed in the last 10 years, an increasing tendency to use a set of markers to detect changes induced by xenobiotics. Several genetic polymorphisms have been cited for the CYP1A1
gene, indicating a lack of functional protein that can cause an increase or a decrease in metabolic activity. The CYP1A1 gene encode the phase I enzymes involved in detoxification of estrogen metabolism, encodes an isoenzyme that catalyzes the oxidation of polycyclic aromatic hydrocarbons (PAHs) in phenolic compounds and epoxides. Mapped and located on the long arm of chromosome 15 (15q22-24). The aim of this study was to analyze the gene polymorphism frequency Mspl CYP1A1m1 with endometriosis. We analyzed 52 samples of peripheral blood of with endometriosis documented by laparoscopy (FÉRTILE) aged 25 to 35 women and 42 samples from women without endometriosis aged 25 to 57 years (control group). Molecular analysis by PCR (polymerase chain reaction). There was a statistically significant association (P = 0.039) between endometriosis and CYP1A1m1 polymorphic allele in women with endometriosis (32.70%) and compared with the control group 14,29%. We conclude that the gene polymorphism
CYP1A1m1 correlates with endometriosis and polymorphisms are W1/m1candcm1/m1 morecfrequentcincpatientscwithcinfertilityandcwithvmorebseverebclinical bpicturebofbendometriosis.
Endometriose é uma enfermidade que afeta entre 10 e 15% das mulheres em idade reprodutiva. Caracterizada pela presença de tecidos semelhante a do endométrio, idênticos aos da cavidade uterina fora do útero. Apesar de algumas definições especificarem que o tecido ectópico funcional é sensível à ação de hormônios e seus mecanismos etiopatogênicos provavelmente envolvem anomalias imunológicas. O grau do comprometimento da endometriose é baseado no sistema proposto pela American Society for Reproductive Medicine (1985), com base nos achados de laparoscopia. Observa-se nos últimos 10 anos a crescente tendência em se utilizar um conjunto de marcadores para detectar alterações induzidas por xenobióticos. Inúmeros polimorfismos genéticos têm sido citados para o gene CYP1A1. O gene codifica enzimas da fase I
envolvidas na desintoxicação no metabolismo de xenobióticos, codifica uma isoenzima que catalisa a oxidação de…
Advisors/Committee Members: Moura, Katia Karina Verolli de Oliveira, Teste, Teste Teste, Silva, Daniela de Melo e.
Subjects/Keywords: Endometriose; Gene CYP1A1; Polimorfismo MspI; Infertilidade; Endometriosis; Gene CYP1A1, MspI Polymorphism; Infertility; CNPQ::CIENCIAS BIOLOGICAS::GENETICA
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APA (6th Edition):
Souza, S. R. d. (2012). Análise do polimorfismo Mspl do gene CYP1A1m1 (Citocromo P450) em mulheres com endometriose. (Masters Thesis). Pontifícia Universidade Católica de Goiás; Genética; PUC Goiás; BR; Ciências Humanas. Retrieved from http://localhost:8080/tede/handle/tede/2352
Chicago Manual of Style (16th Edition):
Souza, Suelene Ribeiro de. “Análise do polimorfismo Mspl do gene CYP1A1m1 (Citocromo P450) em mulheres com endometriose.” 2012. Masters Thesis, Pontifícia Universidade Católica de Goiás; Genética; PUC Goiás; BR; Ciências Humanas. Accessed April 17, 2021.
http://localhost:8080/tede/handle/tede/2352.
MLA Handbook (7th Edition):
Souza, Suelene Ribeiro de. “Análise do polimorfismo Mspl do gene CYP1A1m1 (Citocromo P450) em mulheres com endometriose.” 2012. Web. 17 Apr 2021.
Vancouver:
Souza SRd. Análise do polimorfismo Mspl do gene CYP1A1m1 (Citocromo P450) em mulheres com endometriose. [Internet] [Masters thesis]. Pontifícia Universidade Católica de Goiás; Genética; PUC Goiás; BR; Ciências Humanas; 2012. [cited 2021 Apr 17].
Available from: http://localhost:8080/tede/handle/tede/2352.
Council of Science Editors:
Souza SRd. Análise do polimorfismo Mspl do gene CYP1A1m1 (Citocromo P450) em mulheres com endometriose. [Masters Thesis]. Pontifícia Universidade Católica de Goiás; Genética; PUC Goiás; BR; Ciências Humanas; 2012. Available from: http://localhost:8080/tede/handle/tede/2352
Universidade Estadual de Campinas
6.
Cardoso Filho, Cassio, 1974-.
Associação dos polimorfismos A4889G e T6235C do gene CYP1A1 com características clínicas e epidemiológicas do câncer de mama = Association of CYP1A1 gene polymorphisms (A4889G and T6235C) with clinical and epidemiological features of breast cancer.
Degree: Faculdade de Ciências Médicas; Programa de Pós-Graduação em Tocoginecologia, 2012, Universidade Estadual de Campinas
URL: CARDOSO
FILHO,
Cassio.
Associação
dos
polimorfismos
A4889G
e
T6235C
do
gene
CYP1A1
com
características
clínicas
e
epidemiológicas
do
câncer
de
mama
=
Association
of
CYP1A1
gene
polymorphisms
(A4889G
and
T6235C)
with
clinical
and
epidemiological
features
of
breast
cancer.
2012.
81
f.
Tese
(Doutorado)
-
Universidade
Estadual
de
Campinas,
Faculdade
de
Ciências
Médicas,
Campinas,
SP.
Disponível
em:
<http://www.repositorio.unicamp.br/handle/REPOSIP/310527>.
Acesso
em:
21
ago.
2018.
;
http://repositorio.unicamp.br/jspui/handle/REPOSIP/310527
► Orientadores: Luis Otavio Zanatta Sarian, Maria Salete Costa Gurgel, Carmem Silvia Passos Lima
Tese (Doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made…
(more)
▼ Orientadores: Luis Otavio Zanatta Sarian, Maria Salete Costa Gurgel, Carmem Silvia Passos Lima
Tese (Doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-21T11:21:21Z (GMT). No. of bitstreams: 1 CardosoFilho_Cassio_D.pdf: 1685855 bytes, checksum: 341644d7cc011e51bf31d1f4881e8878 (MD5) Previous issue date: 2012
Resumo: Introdução: A terapêutica sistêmica para o câncer de mama envolve o uso do agente antiestrogênico tamoxifeno, fármaco metabolizado pelo fígado no sistema do citocromo P-450 (CYP). Este, por sua vez, é parcialmente codificado pelo gene CYP1A1, e alguns polimorfismos deste gene têm sido associados com interferências na sua eficácia metabólica. Além disso, diferenças interindividuais no CYP explicam parte das variações na resistência ao tamoxifeno e metabolismo dos estrogênios. Dentre esses polimorfismos, o A4889G (M2) e o T6235C (M1) são conhecidos por afetar a
ativação da estrona e do estradiol, e por provocar a redução da concentração de metabólitos altamente ativos do tamoxifeno, reduzindo teoricamente o efeito antiestrogênico desta modalidade de hormonioterapia no tecido mamário. Embora plausíveis do ponto de vista biológico, as implicações clínicas dos polimorfismos do CYP1A1, ou seja, as características patológicas dos tumores e um pior prognóstico decorrente do aumento dos estrógenos circulantes e redução dos metabólitos ativos do tamoxifeno, não foram ainda avaliadas. Objetivo: Avaliar a associação entre os polimorfismos M1 e M2 do gene CYP1A1 e as características patológicas e clínicas de mulheres com câncer de mama esporádico, em duas abordagens: 1) determinar as associações entre estes polimorfismos e as características patológicas, clínicas e o padrão de sobrevida global em mulheres com câncer de mama esporádico e 2) determinar as associações entre estespolimorfismos e as caracteríasticas patológicas e o comportamento clínico de
tumores de mama com receptores hormonais positivos na vigência do uso de tamoxifeno. Métodos: foram incluídas 741 mulheres com câncer de mama esporádico, 405 das quais com tumores positivos para receptores esteroides e que usaram tamoxifeno como terapia antiestrogênica primária, para as quais os dados referentes a cinco anos de seguimento estavam disponíveis. Foram avaliadas as associações de informações-chave patológicas e clínicas, incluindo a sobrevida geral em cinco anos, com as diferentes combinações de polimorfismos do gene CYP1A1. Resultados: Em mulheres portadoras de ambos os polimorfismos M1 e M2 do CYP1A1, a proporção de tumores grau histológico III (80,3%) foi significativamente menor que nas não-portadoras (89,6%); p ajustado <0,01. O mesmo ocorreu na análise restrita às mulheres com tumores RE+ usando tamoxifeno (76,1% vs. 85,9%; p ajustado= 0,02). Após 60 meses de seguimento, cerca de 75% das mulheres estavam vivas. Não houve diferença significativa na
sobrevivência relacionada com o estado do gene CYP1A1. Conclusões: embora associados a tumores de menor grau histológico, não há…
Advisors/Committee Members: UNIVERSIDADE ESTADUAL DE CAMPINAS, Costa-Gurgel, Maria Salete, 1956-, Lima, Carmen Silvia Passos, 1957-, Sarian, Luís Otávio Zanatta, 1974-, Pinto-Neto, Aarão Mendes, Zeferino, Luiz Carlos, Nazário, Afonso Celso Pinto, Facina, Gil.
Subjects/Keywords: Neoplasias da mama; Polimorfismo; Citocromo P-450 CYP1A1; Sobrevida; Tamoxifeno; Breast neoplasms; Polymorphism; Cytochrome P-450 CYP1A1; Survival; Tamoxifen
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APA ·
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Manager
APA (6th Edition):
Cardoso Filho, Cassio, 1. (2012). Associação dos polimorfismos A4889G e T6235C do gene CYP1A1 com características clínicas e epidemiológicas do câncer de mama = Association of CYP1A1 gene polymorphisms (A4889G and T6235C) with clinical and epidemiological features of breast cancer. (Doctoral Dissertation). Universidade Estadual de Campinas. Retrieved from CARDOSO FILHO, Cassio. Associação dos polimorfismos A4889G e T6235C do gene CYP1A1 com características clínicas e epidemiológicas do câncer de mama = Association of CYP1A1 gene polymorphisms (A4889G and T6235C) with clinical and epidemiological features of breast cancer. 2012. 81 f. Tese (Doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/310527>. Acesso em: 21 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/310527
Chicago Manual of Style (16th Edition):
Cardoso Filho, Cassio, 1974-. “Associação dos polimorfismos A4889G e T6235C do gene CYP1A1 com características clínicas e epidemiológicas do câncer de mama = Association of CYP1A1 gene polymorphisms (A4889G and T6235C) with clinical and epidemiological features of breast cancer.” 2012. Doctoral Dissertation, Universidade Estadual de Campinas. Accessed April 17, 2021.
CARDOSO FILHO, Cassio. Associação dos polimorfismos A4889G e T6235C do gene CYP1A1 com características clínicas e epidemiológicas do câncer de mama = Association of CYP1A1 gene polymorphisms (A4889G and T6235C) with clinical and epidemiological features of breast cancer. 2012. 81 f. Tese (Doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/310527>. Acesso em: 21 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/310527.
MLA Handbook (7th Edition):
Cardoso Filho, Cassio, 1974-. “Associação dos polimorfismos A4889G e T6235C do gene CYP1A1 com características clínicas e epidemiológicas do câncer de mama = Association of CYP1A1 gene polymorphisms (A4889G and T6235C) with clinical and epidemiological features of breast cancer.” 2012. Web. 17 Apr 2021.
Vancouver:
Cardoso Filho, Cassio 1. Associação dos polimorfismos A4889G e T6235C do gene CYP1A1 com características clínicas e epidemiológicas do câncer de mama = Association of CYP1A1 gene polymorphisms (A4889G and T6235C) with clinical and epidemiological features of breast cancer. [Internet] [Doctoral dissertation]. Universidade Estadual de Campinas; 2012. [cited 2021 Apr 17].
Available from: CARDOSO FILHO, Cassio. Associação dos polimorfismos A4889G e T6235C do gene CYP1A1 com características clínicas e epidemiológicas do câncer de mama = Association of CYP1A1 gene polymorphisms (A4889G and T6235C) with clinical and epidemiological features of breast cancer. 2012. 81 f. Tese (Doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/310527>. Acesso em: 21 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/310527.
Council of Science Editors:
Cardoso Filho, Cassio 1. Associação dos polimorfismos A4889G e T6235C do gene CYP1A1 com características clínicas e epidemiológicas do câncer de mama = Association of CYP1A1 gene polymorphisms (A4889G and T6235C) with clinical and epidemiological features of breast cancer. [Doctoral Dissertation]. Universidade Estadual de Campinas; 2012. Available from: CARDOSO FILHO, Cassio. Associação dos polimorfismos A4889G e T6235C do gene CYP1A1 com características clínicas e epidemiológicas do câncer de mama = Association of CYP1A1 gene polymorphisms (A4889G and T6235C) with clinical and epidemiological features of breast cancer. 2012. 81 f. Tese (Doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/310527>. Acesso em: 21 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/310527
University of Pretoria
7.
Van Tonder, Jacob John.
Development of an in vitro mechanistic toxicity
screening model using cultured hepatocytes
.
Degree: 2012, University of Pretoria
URL: http://upetd.up.ac.za/thesis/available/etd-04262012-112100/
► In vitro testing includes both cell-based and cell-free systems that can be used to detect toxicity induced by xenobiotics. In vitro methods are especially useful…
(more)
▼ In vitro testing includes both cell-based and
cell-free systems that can be used to detect toxicity induced by
xenobiotics. In vitro methods are especially useful in rapidly
gathering intelligence regarding the toxicity of compounds for
which none is available such as new chemical entities developed in
the pharmaceutical industry. In addition to this, in vitro
investigations are invaluable in providing information concerning
mechanisms of toxicity of xenobiotics. This type of toxicity
testing has gained popularity among the research and development
community because of a number of advantages such as scalability to
high throughput screening, cost-effectiveness and predictive power.
Hepatotoxicity is one of the major causes of drug attrition and the
high cost associated with drug development poses a heavy burden on
the development of new chemical entities. Early detection of
hepatotoxic agents by in vitro methods will improve lead
optimisation and decrease the cost of drug development and reduce
drug-induced liver injury. Literature highlights the need for a
cellbased in vitro model that is capable of assessing multiple
toxicity parameters, which assesses a wider scope of toxicity and
would be able to detect subtle types of hepatotoxicity. The present
study was aimed at developing an in vitro procedure capable of
mechanistically profiling the effects of known hepatotoxin
dichlorodiphenyl trichloroethane (DDT) and its metabolites,
dichlorodiphenyl dichloroethylene (DDE) and dichlorodiphenyl
dichloroethane (DDD) on an established liver-derived cell line,
HepG2, by evaluating several different aspects of cellular function
using a number of simultaneous in vitro assays on a single 96 well
microplate. Examined parameters have been suggested by the European
Medicines Agency and include: cell viability, phase I metabolism,
oxidative stress, mitochondrial toxicity and mode of cell death
(apoptosis vs. necrosis). To further assess whether the developed
method was capable of detecting hepatoprotection, the effect of the
known hepatoprotectant, N-acetylcysteine, was determined. Viability
decreased in a dose-dependent manner yielding IC50 values of 54 μM,
64 μM and 44 μM for DDT, DDE and DDD, respectively. Evaluation of
phase I metabolism showed that cytochrome P4501A1 activity was
dose-dependently induced. Test compounds decreasedlevels of
reactive oxygen species, and significantly hyperpolarised the
mitochondrialmembrane potential. Assessment of the mode of cell
death revealed a significant elevation of caspase-3 activity, with
DDD proving to be most potent. DDT alone induced dosedependent loss
of membrane integrity. These results suggest that the tested
compounds produce apoptotic death likely due to mitochondrial
toxicity with subsequent caspase-3 activation and apoptotic cell
death. The developed in vitro assay method reduces the time it
would take to assess the tested parameters separately, produces
results from multiple endpoints that broadens the scope of toxicity
compared to single-endpoint methods. In addition to this…
Advisors/Committee Members: Dr A D Cromarty (advisor), Prof M Gulumian (advisor), Prof V Steenkamp (advisor).
Subjects/Keywords: Apoptosis;
Cyp1a1;
Ddd;
Dde;
Ddt;
Hepatotoxicity;
Mechanistic profiling;
UCTD
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Van Tonder, J. J. (2012). Development of an in vitro mechanistic toxicity
screening model using cultured hepatocytes
. (Doctoral Dissertation). University of Pretoria. Retrieved from http://upetd.up.ac.za/thesis/available/etd-04262012-112100/
Chicago Manual of Style (16th Edition):
Van Tonder, Jacob John. “Development of an in vitro mechanistic toxicity
screening model using cultured hepatocytes
.” 2012. Doctoral Dissertation, University of Pretoria. Accessed April 17, 2021.
http://upetd.up.ac.za/thesis/available/etd-04262012-112100/.
MLA Handbook (7th Edition):
Van Tonder, Jacob John. “Development of an in vitro mechanistic toxicity
screening model using cultured hepatocytes
.” 2012. Web. 17 Apr 2021.
Vancouver:
Van Tonder JJ. Development of an in vitro mechanistic toxicity
screening model using cultured hepatocytes
. [Internet] [Doctoral dissertation]. University of Pretoria; 2012. [cited 2021 Apr 17].
Available from: http://upetd.up.ac.za/thesis/available/etd-04262012-112100/.
Council of Science Editors:
Van Tonder JJ. Development of an in vitro mechanistic toxicity
screening model using cultured hepatocytes
. [Doctoral Dissertation]. University of Pretoria; 2012. Available from: http://upetd.up.ac.za/thesis/available/etd-04262012-112100/
8.
Sakai, Kazuaki.
CYP1A1, GSTM1, GSTT1, and TP53 Polymorphisms and Risk of Gallbladder Cancer in Bolivians : ボリビア人におけるCYP1A1、GSTM1、GSTT1、TP53 遺伝子多型と胆嚢がん発症リスク.
Degree: 博士（医学）, 2016, Niigata University / 新潟大学
URL: http://hdl.handle.net/10191/41929
► 学位の種類: 博士（医学）. 報告番号: 甲第4133号. 学位記番号: 新大院博（医）甲第700号. 学位授与年月日: 平成28年3月23日
Asian Pacific Journal of Cancer Prevention. 2016, 17(2), 781-784.
The Plurinational State of Bolivia (Bolivia) has a…
(more)
▼ 学位の種類: 博士（医学）. 報告番号: 甲第4133号. 学位記番号: 新大院博（医）甲第700号. 学位授与年月日: 平成28年3月23日
Asian Pacific Journal of Cancer Prevention. 2016, 17(2), 781-784.
The Plurinational State of Bolivia (Bolivia) has a high incidence rate of gallbladder cancer (GBC). However, the genetic and environmental risk factors for GBC development are not well understood. We aimed to assess whether or not cytochrome P450, (CYP1A1), glutathione S-transferase mu 1 (GSTM1), theta 1 (GSTT1) and tumor suppressor protein p53 (TP53) genetic polymorphisms modulate GBC susceptibility in Bolivians. This case-control study covered32 patients with GBC and 86 healthy subjects. GBC was diagnosed on the basis of histological analysis of tissues at the Instituto de Gastroenterologia Boliviano-Japones (IGBJ); the healthy subjects were members of the staff at the IGBJ. Distributions of the CYP1A1 rs1048943 and TP53 rs1042522 polymorphisms were assayed using PCR-restriction fragment length polymorphism assay. GSTM1 and GSTT1 deletion polymorphisms were detected by a multiplex PCR assay. The frequency of the GSTM1 null genotype was significantly higher in GBC patients than in the healthy subjects (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.03-5.37; age-adjusted OR, 3.53; 95% CI, 1.29-9.66; age- and sex-adjusted OR, 3.40; 95% CI, 1.24-9.34). No significant differences were observed in the frequencies of CYP1A1, GSTT1, or TP53 polymorphisms between the two groups. The GSTM1 null genotype was associated with increased GBC risk in Bolivians. Additional studies with larger control and case populations are warranted to confirm the association between the GSTM1 deletion polymorphism and GBC risk suggested in the present study.
Subjects/Keywords: Gallbladder cancer; genetic susceptibility; CYP1A1; GSTM1; GSTT1; TP53
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APA ·
Chicago ·
MLA ·
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to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sakai, K. (2016). CYP1A1, GSTM1, GSTT1, and TP53 Polymorphisms and Risk of Gallbladder Cancer in Bolivians : ボリビア人におけるCYP1A1、GSTM1、GSTT1、TP53 遺伝子多型と胆嚢がん発症リスク. (Thesis). Niigata University / 新潟大学. Retrieved from http://hdl.handle.net/10191/41929
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Sakai, Kazuaki. “CYP1A1, GSTM1, GSTT1, and TP53 Polymorphisms and Risk of Gallbladder Cancer in Bolivians : ボリビア人におけるCYP1A1、GSTM1、GSTT1、TP53 遺伝子多型と胆嚢がん発症リスク.” 2016. Thesis, Niigata University / 新潟大学. Accessed April 17, 2021.
http://hdl.handle.net/10191/41929.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Sakai, Kazuaki. “CYP1A1, GSTM1, GSTT1, and TP53 Polymorphisms and Risk of Gallbladder Cancer in Bolivians : ボリビア人におけるCYP1A1、GSTM1、GSTT1、TP53 遺伝子多型と胆嚢がん発症リスク.” 2016. Web. 17 Apr 2021.
Vancouver:
Sakai K. CYP1A1, GSTM1, GSTT1, and TP53 Polymorphisms and Risk of Gallbladder Cancer in Bolivians : ボリビア人におけるCYP1A1、GSTM1、GSTT1、TP53 遺伝子多型と胆嚢がん発症リスク. [Internet] [Thesis]. Niigata University / 新潟大学; 2016. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/10191/41929.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Sakai K. CYP1A1, GSTM1, GSTT1, and TP53 Polymorphisms and Risk of Gallbladder Cancer in Bolivians : ボリビア人におけるCYP1A1、GSTM1、GSTT1、TP53 遺伝子多型と胆嚢がん発症リスク. [Thesis]. Niigata University / 新潟大学; 2016. Available from: http://hdl.handle.net/10191/41929
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Alberta
9.
Amara, Issa.
Modulation of Aryl Hydrocarbon Receptor Regulated-Genes by
Mercury.
Degree: PhD, Faculty of Pharmacy and Pharmaceutical
Sciences, 2013, University of Alberta
URL: https://era.library.ualberta.ca/files/4m90dv732
► Aryl hydrocarbon receptor (AhR) ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and metals, such as mercury (Hg), are environmental co-contaminants with multiple biological consequences. Therefore, the objectives…
(more)
▼ Aryl hydrocarbon receptor (AhR) ligands such as
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and metals, such as
mercury (Hg), are environmental co-contaminants with multiple
biological consequences. Therefore, the objectives of the current
dissertation were to: 1) examine the potential effect of
co-exposure to Hg and TCDD on the expression of the AhR-regulated
phase I and phase II genes in HepG2 cells, isolated mouse
hepatocytes, and in vivo in the liver, kidney, lung, and heart of
C57Bl/6J mice, and 2) to explore the molecular mechanisms involved
in this modulation. In vitro, Hg2+ significantly inhibited the
TCDD-mediated induction of CYP1A1 at the mRNA, protein, and
catalytic activity levels. Furthermore, co-exposure to Hg2+ and
TCDD significantly decreased the TCDD-mediated induction of
AhR-dependent luciferase reporter gene expression. At the
post-translational level, Hg2+ significantly decreased the protein
half-life, and increased the expression of heme oxygenase-1 (HO-1),
which coincided with further decrease in the CYP1A1 catalytic
activity levels. With regard to NQO1, Hg2+ increased its expression
at the mRNA, protein, and activity levels in the absence and
presence of both NQO1 inducers, TCDD and Sulforaphane (SUL), which
coincided with increased nuclear accumulation of Nrf2 protein. Hg2+
was able to induce the antioxidant responsive element
(ARE)-dependent luciferase reporter gene expression in an Nrf2
dependent mechanism. In vivo, Hg2+ differentially modulated phase I
and phase II AhR-regulated genes at the constitutive and inducible
levels. Interestingly, Hg2+ increased serum hemoglobin (Hb) levels
in mice treated for 24 h with Hg2+. Upon treatment of isolated
hepatocytes with Hb alone, there was an increase in the
AhR-dependent luciferase activity with a subsequent increase in
Cyp1a1 protein and catalytic activity levels. In conclusion, the
present study demonstrates that exposure to Hg2+ and TCDD in vitro
may decrease TCDD-mediated carcinogenicity by decreasing the
induction of CYP1A1 and increasing the induction of NQO1. However;
at the in vivo level, Hg2+ modulates the constitutive and inducible
AhR-regulated genes in a time-, tissue- and, AhR-regulated enzyme
specific manner. In addition, at the in vitro level HO-1 and Nrf2
are involved in the modulation of CYP1A1 and NQO1 respectively,
while Hb was implicated as an in vivo specific modulator of
Cyps.
Subjects/Keywords: AhR, Mercury, TCDD CYP1A1, NQO1, in vitro and in
vivo
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APA (6th Edition):
Amara, I. (2013). Modulation of Aryl Hydrocarbon Receptor Regulated-Genes by
Mercury. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/4m90dv732
Chicago Manual of Style (16th Edition):
Amara, Issa. “Modulation of Aryl Hydrocarbon Receptor Regulated-Genes by
Mercury.” 2013. Doctoral Dissertation, University of Alberta. Accessed April 17, 2021.
https://era.library.ualberta.ca/files/4m90dv732.
MLA Handbook (7th Edition):
Amara, Issa. “Modulation of Aryl Hydrocarbon Receptor Regulated-Genes by
Mercury.” 2013. Web. 17 Apr 2021.
Vancouver:
Amara I. Modulation of Aryl Hydrocarbon Receptor Regulated-Genes by
Mercury. [Internet] [Doctoral dissertation]. University of Alberta; 2013. [cited 2021 Apr 17].
Available from: https://era.library.ualberta.ca/files/4m90dv732.
Council of Science Editors:
Amara I. Modulation of Aryl Hydrocarbon Receptor Regulated-Genes by
Mercury. [Doctoral Dissertation]. University of Alberta; 2013. Available from: https://era.library.ualberta.ca/files/4m90dv732
Université Laval
10.
Zarifi Khosroshahi, Mitra.
Study of the hepatic stability and the therapeutic
potential of novel antimitotic prodrugs selective for
CYP1A1-expressing breast cancer cells.
Degree: 2019, Université Laval
URL: http://hdl.handle.net/20.500.11794/36900
► Nous avons récemment découvert et étudié une nouvelle classe d'agents antimicrotubules appelés phényl 4-(2-oxo-3-alkylimidazolidin-1-yl)benzènesulfonates (PAIB-SOs) hautement actifs et sélectifs pour les cellules cancéreuses du sein.…
(more)
▼ Nous avons récemment découvert et étudié une
nouvelle classe d'agents antimicrotubules appelés phényl
4-(2-oxo-3-alkylimidazolidin-1-yl)benzènesulfonates (PAIB-SOs)
hautement actifs et sélectifs pour les cellules cancéreuses du
sein. Leur mécanisme de sélectivité est basé sur la métabolisation
des PAIB-SOs par le CYP1A1 en agents antimitotiques puissants
appelés phényl 4-(2-oxo-3-imidazolidin-1-yl)benzènesulfonates
(PIB-SOs). L'objectif principal de ma recherche était d'évaluer la
période nécessaire à l’induction d’une activité cytotoxique
significative de quelques-uns de ces PAIB-SOs prometteurs sur les
cellules cancéreuses du sein. Dans un second volet, nous désirions
étudier la stabilité métabolique et la cinétique de bioactivation
par le CYP1A1 de 8 PAIB-SOs phare en vue d’en sélectionner 4 pour
des essais sur des animaux. Premièrement, nos études ont montré que
l'activité antiproliférative des PAIB-SOs est concentration et
temps dépendante. Un temps de contact des PAIB-SOs étudiés avec les
cellules cancéreuses du sein variant de 24 à 36 h est nécessaire
pour observer une activité antiproliférative significative.
Deuxièmement, nous avons confirmé que tous les PAIB-SOs évalués
sont rapidement biotransformés en présence de CYP1A1 en PIB-SOs.
Troisièmement, les expériences de stabilité hépatique des PAIB-SOs
incubés avec des microsomes soit humains, de souris ou de rats ont
montré que leur demi-vie et leur clairance intrinsèque varient
selon la structure du PAIB-SO et l’espèce animale étudiée. La
stabilité des PAIB-SOs incubés avec des microsomes de souris est
plus faible que lorsqu’incubé avec des microsomes humains ou de
rats. De plus, la stabilité métabolique de ces PAIB-SOs avec les
microsomes humains ou de rats est similaire. Le criblage de notre
chimiothèque a permis d’identifier les CEU-829, -938, -934 et -913
comme étant les PAIB-SOs métaboliquement les plus stables et
générant les plus basses concentrations de PIB-SOs avec des
demi-vies respectives de 22, 55, 31 et 41 minutes dans les
microsomes humains, de 43, 52, 23 et 44 minutes dans les microsomes
de rat et de 3,7, 20, 12 et 1,6 minutes dans les microsomes de
souris. Nos études ont également mis en évidence les CEU-934 et
-938 comme des molécules candidates prometteuses pour des études de
pharmacocinétique et de pharmacodynamie chez la souris et les
CEU-829 et -913 chez les rats.
We recently found and studied a new class of
antimicrotubule agents named phenyl 4-(2-oxo-3-
alkylimidazolidin-1-yl)benzenesulfonates (PAIB-SOs) that are highly
active and selective to breast cancer cells. PAIB-SOs are the first
antimicrotuble CYP1A1-dependent prodrugs and their mechanism of
selectivity is based on the metabolization in human breast cancer
cells of PAIB-SOs by CYP1A1 into potent antimitotics named phenyl
4-(2-oxoimidazolidin-1-yl)benzenesulfonates (PIB-SOs). The main
objective of my research was to evaluate the period necessary to
trigger an efficient antiproliferative activity on breast cancer
cells and to study the metabolic stability and the kinetics of…
Advisors/Committee Members: Fortin, Sébastien, Gobeil, Stéphane.
Subjects/Keywords: Anticancéreux; Cytochrome P-450 CYP1A1; Sein – Cancer; Cellules cancéreuses
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MLA ·
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CSE |
Export
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Manager
APA (6th Edition):
Zarifi Khosroshahi, M. (2019). Study of the hepatic stability and the therapeutic
potential of novel antimitotic prodrugs selective for
CYP1A1-expressing breast cancer cells. (Thesis). Université Laval. Retrieved from http://hdl.handle.net/20.500.11794/36900
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Zarifi Khosroshahi, Mitra. “Study of the hepatic stability and the therapeutic
potential of novel antimitotic prodrugs selective for
CYP1A1-expressing breast cancer cells.” 2019. Thesis, Université Laval. Accessed April 17, 2021.
http://hdl.handle.net/20.500.11794/36900.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Zarifi Khosroshahi, Mitra. “Study of the hepatic stability and the therapeutic
potential of novel antimitotic prodrugs selective for
CYP1A1-expressing breast cancer cells.” 2019. Web. 17 Apr 2021.
Vancouver:
Zarifi Khosroshahi M. Study of the hepatic stability and the therapeutic
potential of novel antimitotic prodrugs selective for
CYP1A1-expressing breast cancer cells. [Internet] [Thesis]. Université Laval; 2019. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/20.500.11794/36900.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Zarifi Khosroshahi M. Study of the hepatic stability and the therapeutic
potential of novel antimitotic prodrugs selective for
CYP1A1-expressing breast cancer cells. [Thesis]. Université Laval; 2019. Available from: http://hdl.handle.net/20.500.11794/36900
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Pretoria
11.
Van Tonder, Jacob
John.
Development of
an in vitro mechanistic toxicity screening model using cultured
hepatocytes.
Degree: Pharmacology, 2011, University of Pretoria
URL: http://hdl.handle.net/2263/24162
► In vitro testing includes both cell-based and cell-free systems that can be used to detect toxicity induced by xenobiotics. In vitro methods are especially useful…
(more)
▼ In vitro testing includes both cell-based and cell-free
systems that can be used to detect toxicity induced by xenobiotics.
In vitro methods are especially useful in rapidly gathering
intelligence regarding the toxicity of compounds for which none is
available such as new chemical entities developed in the
pharmaceutical industry. In addition to this, in vitro
investigations are invaluable in providing information concerning
mechanisms of toxicity of xenobiotics. This type of toxicity
testing has gained popularity among the research and development
community because of a number of advantages such as scalability to
high throughput screening, cost-effectiveness and predictive power.
Hepatotoxicity is one of the major causes of drug attrition and the
high cost associated with drug development poses a heavy burden on
the development of new chemical entities. Early detection of
hepatotoxic agents by in vitro methods will improve lead
optimisation and decrease the cost of drug development and reduce
drug-induced liver injury. Literature highlights the need for a
cellbased in vitro model that is capable of assessing multiple
toxicity parameters, which assesses a wider scope of toxicity and
would be able to detect subtle types of hepatotoxicity. The present
study was aimed at developing an in vitro procedure capable of
mechanistically profiling the effects of known hepatotoxin
dichlorodiphenyl trichloroethane (DDT) and its metabolites,
dichlorodiphenyl dichloroethylene (DDE) and dichlorodiphenyl
dichloroethane (DDD) on an established liver-derived cell line,
HepG2, by evaluating several different aspects of cellular function
using a number of simultaneous in vitro assays on a single 96 well
microplate. Examined parameters have been suggested by the European
Medicines Agency and include: cell viability, phase I metabolism,
oxidative stress, mitochondrial toxicity and mode of cell death
(apoptosis vs. necrosis). To further assess whether the developed
method was capable of detecting hepatoprotection, the effect of the
known hepatoprotectant, N-acetylcysteine, was determined. Viability
decreased in a dose-dependent manner yielding IC50 values of 54 μM,
64 μM and 44 μM for DDT, DDE and DDD, respectively. Evaluation of
phase I metabolism showed that cytochrome P4501A1 activity was
dose-dependently induced. Test compounds decreasedlevels of
reactive oxygen species, and significantly hyperpolarised the
mitochondrialmembrane potential. Assessment of the mode of cell
death revealed a significant elevation of caspase-3 activity, with
DDD proving to be most potent. DDT alone induced dosedependent loss
of membrane integrity. These results suggest that the tested
compounds produce apoptotic death likely due to mitochondrial
toxicity with subsequent caspase-3 activation and apoptotic cell
death. The developed in vitro assay method reduces the time it
would take to assess the tested parameters separately, produces
results from multiple endpoints that broadens the scope of toxicity
compared to single-endpoint methods. In addition to this…
Advisors/Committee Members: Cromarty, Allan Duncan (advisor), Gulumian, Mary (advisor), Steenkamp, Vanessa (advisor).
Subjects/Keywords: Apoptosis;
Cyp1a1;
Ddd;
Dde;
Ddt;
Hepatotoxicity; Mechanistic
profiling;
UCTD
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Van Tonder, J. (2011). Development of
an in vitro mechanistic toxicity screening model using cultured
hepatocytes. (Doctoral Dissertation). University of Pretoria. Retrieved from http://hdl.handle.net/2263/24162
Chicago Manual of Style (16th Edition):
Van Tonder, Jacob. “Development of
an in vitro mechanistic toxicity screening model using cultured
hepatocytes.” 2011. Doctoral Dissertation, University of Pretoria. Accessed April 17, 2021.
http://hdl.handle.net/2263/24162.
MLA Handbook (7th Edition):
Van Tonder, Jacob. “Development of
an in vitro mechanistic toxicity screening model using cultured
hepatocytes.” 2011. Web. 17 Apr 2021.
Vancouver:
Van Tonder J. Development of
an in vitro mechanistic toxicity screening model using cultured
hepatocytes. [Internet] [Doctoral dissertation]. University of Pretoria; 2011. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/2263/24162.
Council of Science Editors:
Van Tonder J. Development of
an in vitro mechanistic toxicity screening model using cultured
hepatocytes. [Doctoral Dissertation]. University of Pretoria; 2011. Available from: http://hdl.handle.net/2263/24162
Université de Sherbrooke
12.
Doyon, Kathy.
Clonage de gènes de petits vertébrés susceptibles de voir leur expression induite par des pesticides environnementaux et séquençage et assemblage du génome de l'hirondelle bicolore (Tachycineta bicolor).
Degree: 2015, Université de Sherbrooke
URL: http://hdl.handle.net/11143/6869
► Environ 3500 tonnes de pesticides sont étendues chaque année sur les terres agricoles du Québec. L’utilisation de plusieurs de ces substances a été interdite, car…
(more)
▼ Environ 3500 tonnes de pesticides sont étendues chaque année sur les terres agricoles du Québec. L’utilisation de plusieurs de ces substances a été interdite, car les ingrédients actifs qui les composaient avaient des effets toxiques sur les humains et/ou l’environnement. Malheureusement, certains qui sont toujours en vente ont aussi des effets secondaires non désirables. En effet, ces molécules exogènes ont le potentiel de moduler l’activation de protéines régulatrices comme le récepteur aux dioxines (AhR). AhR active, entre autres, l’expression de gènes faisant partie de la famille du cytochrome P450 (
CYP1A1 et CYP1B1) qui sont impliqués dans la détoxification. Or, dans certains cas, ces enzymes mènent à la production de molécules mutagènes en augmentant la toxicité des ingrédients actifs en les métabolisant.
Le projet global dans lequel s’insère ce projet de maîtrise vise à déterminer les effets génomiques des pesticides environnementaux sur des organismes vivants en milieu naturel dans les environs de la région de l’Estrie. Les espèces choisies comme modèles d’étude sont des insectivores, car les pesticides s’accumulent dans les lipides et que les insectes en sont une excellente source. Les consommateurs d’insectes sont donc d’excellents marqueurs du niveau de contamination de leur environnement par les pesticides. Les deux espèces sélectionnées sont l’hirondelle bicolore (Tachycineta bicolor) et la grande musaraigne (Blarina brevicauda).
De façon plus spécifique, le projet de maîtrise se divise en deux principaux objectifs. Le premier objectif est de valider que les pesticides présents dans l’environnement sont en concentration suffisante pour modifier la régulation génétique d’animaux en milieu naturel. Cette validation se fera en comparant le taux d’expression de
CYP1A1 et CYP1B1 (suite de leur activation par AhR) chez des bêtes ayant été exposées (ou non) à des pesticides. Comme le génome des deux modèles d’étude n’est pas encore séquencé, le clonage partiel des gènes à étudier (AhR et CYP1) a été entamé de même que la conception d’amorces qui permettra de quantifier le niveau d’expression de ces gènes par des réactions en chaîne par polymérase en temps réel (qPCR). À ce jour, une partie de la séquence d’AhR, de CYP1B1 et de trois gènes contrôles ont été séquencés pour l’hirondelle, ce qui a permis de concevoir des amorces pour la quantification de l’expression d’AhR et de deux contrôles. Pour la musaraigne, ce sont les gènes AhR, potentiellement
CYP1A1 et trois contrôles qui ont été séquencés partiellement et ce sont les gènes AhR et les contrôles pour lesquels des amorces sont prêtes à être utilisées pour la quantification par qPCR.
Le deuxième objectif est d’observer les effets génétiques des pesticides de manière globale sur des organismes vivants. Un génome de référence est donc nécessaire pour identifier les régions qui vont être régulées (directement ou indirectement) par les polluants d’origine agricole. Pour la grande musaraigne, c’est le génome de la musaraigne commune (Sorex araneus) qui sera…
Advisors/Committee Members: Gaudreau, Luc R. (advisor), Pelletier, Fanie (advisor).
Subjects/Keywords: AhR; CYP1A1; CYP1B1; Régulation génique; Pesticides; Blarina brevicauda; Tachycineta bicolor
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APA (6th Edition):
Doyon, K. (2015). Clonage de gènes de petits vertébrés susceptibles de voir leur expression induite par des pesticides environnementaux et séquençage et assemblage du génome de l'hirondelle bicolore (Tachycineta bicolor). (Masters Thesis). Université de Sherbrooke. Retrieved from http://hdl.handle.net/11143/6869
Chicago Manual of Style (16th Edition):
Doyon, Kathy. “Clonage de gènes de petits vertébrés susceptibles de voir leur expression induite par des pesticides environnementaux et séquençage et assemblage du génome de l'hirondelle bicolore (Tachycineta bicolor).” 2015. Masters Thesis, Université de Sherbrooke. Accessed April 17, 2021.
http://hdl.handle.net/11143/6869.
MLA Handbook (7th Edition):
Doyon, Kathy. “Clonage de gènes de petits vertébrés susceptibles de voir leur expression induite par des pesticides environnementaux et séquençage et assemblage du génome de l'hirondelle bicolore (Tachycineta bicolor).” 2015. Web. 17 Apr 2021.
Vancouver:
Doyon K. Clonage de gènes de petits vertébrés susceptibles de voir leur expression induite par des pesticides environnementaux et séquençage et assemblage du génome de l'hirondelle bicolore (Tachycineta bicolor). [Internet] [Masters thesis]. Université de Sherbrooke; 2015. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/11143/6869.
Council of Science Editors:
Doyon K. Clonage de gènes de petits vertébrés susceptibles de voir leur expression induite par des pesticides environnementaux et séquençage et assemblage du génome de l'hirondelle bicolore (Tachycineta bicolor). [Masters Thesis]. Université de Sherbrooke; 2015. Available from: http://hdl.handle.net/11143/6869
Université de Sherbrooke
13.
Bergeron, Sandra.
Effets d'un mélange d'ingrédients actifs de pesticides sur l'activation de la voie du récepteur aux hydrocarbures d'aryle.
Degree: 2017, Université de Sherbrooke
URL: http://hdl.handle.net/11143/11066
► Depuis bon nombre d’années déjà, la question ne se pose plus ; l’utilisation des pesticides en agriculture est nécessaire puisque sans ces derniers les chances…
(more)
▼ Depuis bon nombre d’années déjà, la question ne se pose plus ; l’utilisation des pesticides en agriculture est nécessaire puisque sans ces derniers les chances que les terres soient ravagées par les insectes, champignons ou petits rongeurs représenteraient un trop grand risque pour les agriculteurs. Cependant, cette utilisation massive de pesticides en agriculture apporte son lot de questionnements et d’inquiétudes face aux effets néfastes qu’ils pourraient avoir tant sur les humains que sur la faune et la flore. Bien que tous les pesticides utilisés au Canada soient homologués par Santé Canada, et sont donc jugés comme ne représentant pas de risques élevés ni pour l’environnement ni les humains, nul ne connait les effets d’un mélange de pesticides sur nos cellules, notre organisme. Ce projet de recherche vise donc à évaluer les effets d’un mélange de pesticides composé de cinq ingrédients actifs communément utilisés en agriculture sur les niveaux d’expression du gène
CYP1A1, un gène cible du récepteur aux hydrocarbures d'aryle (AhR).
Ce récepteur, bien qu’impliqué dans bon nombre d’autres réponses cellulaires, joue un rôle important dans la détoxification de l’organisme en activant la transcription de certains gènes dans la famille du cytochrome P450, dont le gène
CYP1A1. Tel que mentionné précédemment, le but du présent projet de recherche est d’évaluer les effets d’un mélange composé d’au moins deux ingrédients actifs de pesticides sur l’activation de la voie de AhR. Les résultats du projet de recherche ont démontré que certaines combinaisons donnent lieu à une activation synergique de la voie AhR alors que d’autres donnent plutôt lieu à une activation additive. Dans le cas où la concentration des ingrédients actifs est élevée, on obtient plutôt un effet inhibiteur. N’est-ce pas paradoxal qu’à faibles doses, il y a un effet soit additif ou synergique alors qu’à de hautes concentrations, l’effet est plutôt inhibiteur ? Il ne faut alors pas croire que de fortes doses de pesticides sont bénéfiques puisque les effets sur les niveaux d’expression des gènes cibles de AhR ne signifient pas qu’il en sera de même pour les tous les autres gènes. Les résultats ont également démontré qu’en présence d’œstrogène, les ingrédients actifs seuls ou en combinaison ont le même effet que le 2,3,7,8-Tétrachlorodibenzo-para-dioxine (TCDD) sur l’interaction croisée entre AhR et le récepteur aux œstrogènes ; l’expression du gène
CYP1A1 est réprimée alors que l’expression de CYP1B1 demeure inchangée.
Maintenant qu’on comprend bien les effets que peuvent avoir une combinaison d’ingrédients actifs de pesticides sur l’activation AhR, il ne reste plus qu’à comprendre pourquoi certains mélanges donnent lieu à une activation synergique et d’autres additive. Une question bien simple, mais à laquelle il est si difficile de répondre.
Advisors/Committee Members: Gaudreau, Luc R. (advisor).
Subjects/Keywords: AhR; CYP1A1; CYP1B1; ERα; MCF-7; Interaction croisée; Pesticides; Transcription génique
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Bergeron, S. (2017). Effets d'un mélange d'ingrédients actifs de pesticides sur l'activation de la voie du récepteur aux hydrocarbures d'aryle. (Masters Thesis). Université de Sherbrooke. Retrieved from http://hdl.handle.net/11143/11066
Chicago Manual of Style (16th Edition):
Bergeron, Sandra. “Effets d'un mélange d'ingrédients actifs de pesticides sur l'activation de la voie du récepteur aux hydrocarbures d'aryle.” 2017. Masters Thesis, Université de Sherbrooke. Accessed April 17, 2021.
http://hdl.handle.net/11143/11066.
MLA Handbook (7th Edition):
Bergeron, Sandra. “Effets d'un mélange d'ingrédients actifs de pesticides sur l'activation de la voie du récepteur aux hydrocarbures d'aryle.” 2017. Web. 17 Apr 2021.
Vancouver:
Bergeron S. Effets d'un mélange d'ingrédients actifs de pesticides sur l'activation de la voie du récepteur aux hydrocarbures d'aryle. [Internet] [Masters thesis]. Université de Sherbrooke; 2017. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/11143/11066.
Council of Science Editors:
Bergeron S. Effets d'un mélange d'ingrédients actifs de pesticides sur l'activation de la voie du récepteur aux hydrocarbures d'aryle. [Masters Thesis]. Université de Sherbrooke; 2017. Available from: http://hdl.handle.net/11143/11066
14.
Carmen-Veronica Naira Obianwu.
Characterization of serum-induced CYP1A1 expression and activity in mouse embryo fibroblasts.
Degree: MS, Pharmacology and Toxicology, 2005, The University of Texas Medical Branch
URL: http://hdl.handle.net/2152.3/192
► The AhR is a ligand-activated transcription factor that mediates the toxic effects of environmental contaminants that include TCDD. Using a TCDD dose-response treatment in MEFs,…
(more)
▼ The AhR is a ligand-activated transcription factor that mediates the toxic effects of environmental contaminants that include TCDD. Using a TCDD dose-response treatment in MEFs, we observed a super induction of
CYP1A1 with newborn calf serum (NCS) in the presence (10nM/15nM) of TCDD. In addition to NCS, fetal bovine serum (FBS) also has the capability to yield a
CYP1A1 super induction. These results suggest that components within the sera affect the activity of the AhR and consequent
CYP1A1 expression. To pursue this idea, characterization of the serum factors were investigated. The findings indicated that serum factor(s) in both sera are heat sensitive at 50◦C, withstand removal from charcoal stripping sera and are ¡Ý 10,000 kDa in size. Using RT-PCR, we found that NCS factors only, could super induce
CYP1A1 at the gene level. Moreover, MEFs are the only cells observed in this study that are susceptible to
CYP1A1 super induction.
Advisors/Committee Members: Cornelis Elferink Ph.D. (advisor), Xiaodong Cheng Ph.D. (committee member), Jonathan B. Ward Ph.D. (committee member).
Subjects/Keywords: TCDD; serum; CYP1A1; AHR
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APA ·
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MLA ·
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APA (6th Edition):
Obianwu, C. N. (2005). Characterization of serum-induced CYP1A1 expression and activity in mouse embryo fibroblasts. (Masters Thesis). The University of Texas Medical Branch. Retrieved from http://hdl.handle.net/2152.3/192
Chicago Manual of Style (16th Edition):
Obianwu, Carmen-Veronica Naira. “Characterization of serum-induced CYP1A1 expression and activity in mouse embryo fibroblasts.” 2005. Masters Thesis, The University of Texas Medical Branch. Accessed April 17, 2021.
http://hdl.handle.net/2152.3/192.
MLA Handbook (7th Edition):
Obianwu, Carmen-Veronica Naira. “Characterization of serum-induced CYP1A1 expression and activity in mouse embryo fibroblasts.” 2005. Web. 17 Apr 2021.
Vancouver:
Obianwu CN. Characterization of serum-induced CYP1A1 expression and activity in mouse embryo fibroblasts. [Internet] [Masters thesis]. The University of Texas Medical Branch; 2005. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/2152.3/192.
Council of Science Editors:
Obianwu CN. Characterization of serum-induced CYP1A1 expression and activity in mouse embryo fibroblasts. [Masters Thesis]. The University of Texas Medical Branch; 2005. Available from: http://hdl.handle.net/2152.3/192
15.
Geromini, Katherine.
A Test of the Hypothesis That Environmental Chemicals Interfere With Thyroid Hormone Action in Human Placenta.
Degree: MS, Molecular & Cellular Biology, 2012, University of Massachusetts
URL: https://scholarworks.umass.edu/theses/772
► Thyroid hormone is essential for normal brain development and recognition of this has led to universal screening of newborns for thyroid function to ensure…
(more)
▼ Thyroid hormone is essential for normal brain development and recognition of this has led to universal screening of newborns for thyroid function to ensure that circulating levels of thyroid hormone are within a range known to be supportive of normal growth and mental development. Environmental chemicals that interfere with thyroid function are known to inhibit normal growth and mental development. Work from our lab and from labs internationally demonstrates in animal systems that some industrial chemicals such as PCBs, PBDEs, and others may interact with the thyroid hormone receptor(s) in ways that are not predicted by changes in serum thyroid hormone levels. Our work demonstrates that the enzyme
CYP1A1 must metabolize some individual PCB congeners before they can interact with the thyroid receptor. In animals, this requirement appears to be manifested in part by a strong correlation between
CYP1A1 and TH target gene expression. Here we present that this pattern extends to humans by demonstrating a correlation between increased
CYP1A1 mRNA and an abundance of thyroid hormone responsive gene mRNA.
Advisors/Committee Members: Thomas Zoeller.
Subjects/Keywords: endocrine disruption; thyroid hormone; placenta; cyp1a1; Molecular Biology
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APA (6th Edition):
Geromini, K. (2012). A Test of the Hypothesis That Environmental Chemicals Interfere With Thyroid Hormone Action in Human Placenta. (Masters Thesis). University of Massachusetts. Retrieved from https://scholarworks.umass.edu/theses/772
Chicago Manual of Style (16th Edition):
Geromini, Katherine. “A Test of the Hypothesis That Environmental Chemicals Interfere With Thyroid Hormone Action in Human Placenta.” 2012. Masters Thesis, University of Massachusetts. Accessed April 17, 2021.
https://scholarworks.umass.edu/theses/772.
MLA Handbook (7th Edition):
Geromini, Katherine. “A Test of the Hypothesis That Environmental Chemicals Interfere With Thyroid Hormone Action in Human Placenta.” 2012. Web. 17 Apr 2021.
Vancouver:
Geromini K. A Test of the Hypothesis That Environmental Chemicals Interfere With Thyroid Hormone Action in Human Placenta. [Internet] [Masters thesis]. University of Massachusetts; 2012. [cited 2021 Apr 17].
Available from: https://scholarworks.umass.edu/theses/772.
Council of Science Editors:
Geromini K. A Test of the Hypothesis That Environmental Chemicals Interfere With Thyroid Hormone Action in Human Placenta. [Masters Thesis]. University of Massachusetts; 2012. Available from: https://scholarworks.umass.edu/theses/772
16.
Kleber Santiago Freitas e Silva.
POLIMORFISMOS GENÉTICOS EM PACIENTES DE GOIÂNIA COM ENDOMETRIOSE: UM ESTUDO ANALÍTICO.
Degree: 2013, Pontifícia Universidade Católica de Goiás
URL: http://tede.biblioteca.ucg.br/tde_busca/arquivo.php?codArquivo=1309
► Controles intra e extracelulares impedem a implantação e a proliferação de células endometriais ectópicas nas mulheres saudáveis. Anormalidades em quaisquer desses controles levam à sobrevida…
(more)
▼ Controles intra e extracelulares impedem a implantação e a proliferação de células endometriais ectópicas nas mulheres saudáveis. Anormalidades em quaisquer desses controles levam à sobrevida dessas células, implantação e a consequente progressão da Endometriose. Células endometriais com polimorfismos genéticos respondem a sinais locais e se proliferam não sofrendo apoptose. Os produtos dessas células anormais estimulam a invasão de tecidos e induzem respostas inflamatórias. A doença é complexa e relacionada a fatores como o genético, o imunológico e o ambiental. Este trabalho analisou seis polimorfismos de seis diferentes genes (p53; Receptor β de estrógeno; Receptor de progesterona; GSTM1; GSTT1;
CYP1A1). As frequências dos genótipos polimórficos foram obtidas das mesmas 50 pacientes para todos os genes e analisadas pelo Teste Exato de Fisher ou Teste G. Os genes foram analisados dois a dois e posteriormente três a três. Resultados significativos foram encontrados para seis pares de genes (p53- REβ com frequência de polimorfismo 5,9 vezes maior no grupo endometriose; p53-GSTM1 com frequência 2,39 vezes maior; p53-
CYP1A1 com 65,5% das pacientes com endometriose apresentando os polimorfismos; REβ-PROGINS com frequência 3,0 vezes maior; GSTM1-PROGINS e GSTT1-
CYP1A1, ambos com 31,25% das pacientes do grupo endometriose apresentando os polimorfismos). Em 15 situações quando os genes foram analisados três a três o p foi menor que 0,05. Os polimorfismos de maior frequência foram dos genes p53, REβ e GSTM1 com 20% das pacientes com endometriose apresentando esses polimorfismos; PROGINS, REβ e GSTM1 com 18% e p53, REβ e PROGINS com 12%. Esses resultados corroboram a ideia de que a presença de polimorfismos em mais de um gene relacionado à endometriose pode levar ao aparecimento e deselvolvimento da doença. Estudos devem ser direcionados a esses genes na tentativa de compreender mellhor a relação entre eles e o possível desenvolvimento de novas técnicas de diagnóstico baseada nos marcadores moleculares desses mesmos genes.
Advisors/Committee Members: Katia Karina Verolli de Oliveira Moura.
Subjects/Keywords: Polimorfismo; p53; Receptor β; de estrógeno; Receptor de progesterona; GSTM1; GSTT1; CYP1A1; Endometriose; GENETICA; Polymorphism; p53; Estrogen Receptor β; Progesterone receptor; GSTM1; GSTT1; CYP1A1; Endometriosis
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APA ·
Chicago ·
MLA ·
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CSE |
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to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Silva, K. S. F. e. (2013). POLIMORFISMOS GENÉTICOS EM PACIENTES DE GOIÂNIA COM ENDOMETRIOSE: UM ESTUDO ANALÍTICO. (Thesis). Pontifícia Universidade Católica de Goiás. Retrieved from http://tede.biblioteca.ucg.br/tde_busca/arquivo.php?codArquivo=1309
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Silva, Kleber Santiago Freitas e. “POLIMORFISMOS GENÉTICOS EM PACIENTES DE GOIÂNIA COM ENDOMETRIOSE: UM ESTUDO ANALÍTICO.” 2013. Thesis, Pontifícia Universidade Católica de Goiás. Accessed April 17, 2021.
http://tede.biblioteca.ucg.br/tde_busca/arquivo.php?codArquivo=1309.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Silva, Kleber Santiago Freitas e. “POLIMORFISMOS GENÉTICOS EM PACIENTES DE GOIÂNIA COM ENDOMETRIOSE: UM ESTUDO ANALÍTICO.” 2013. Web. 17 Apr 2021.
Vancouver:
Silva KSFe. POLIMORFISMOS GENÉTICOS EM PACIENTES DE GOIÂNIA COM ENDOMETRIOSE: UM ESTUDO ANALÍTICO. [Internet] [Thesis]. Pontifícia Universidade Católica de Goiás; 2013. [cited 2021 Apr 17].
Available from: http://tede.biblioteca.ucg.br/tde_busca/arquivo.php?codArquivo=1309.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Silva KSFe. POLIMORFISMOS GENÉTICOS EM PACIENTES DE GOIÂNIA COM ENDOMETRIOSE: UM ESTUDO ANALÍTICO. [Thesis]. Pontifícia Universidade Católica de Goiás; 2013. Available from: http://tede.biblioteca.ucg.br/tde_busca/arquivo.php?codArquivo=1309
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
17.
Silva, Kleber Santiago Freitas e.
POLIMORFISMOS GENÉTICOS EM PACIENTES DE GOIÂNIA COM ENDOMETRIOSE: UM ESTUDO ANALÍTICO.
Degree: 2013, Pontifícia Universidade Católica de Goiás; Genética; PUC Goiás; BR; Ciências Humanas
URL: http://localhost:8080/tede/handle/tede/2366
► Made available in DSpace on 2016-08-10T10:38:42Z (GMT). No. of bitstreams: 1 KLEBER SANTIAGO FREITAS E SILVA.pdf: 1080005 bytes, checksum: 9dfcb821b9cd1574718e2442cabc533b (MD5) Previous issue date: 2013-02-18…
(more)
▼ Made available in DSpace on 2016-08-10T10:38:42Z (GMT). No. of bitstreams: 1 KLEBER SANTIAGO FREITAS E SILVA.pdf: 1080005 bytes, checksum: 9dfcb821b9cd1574718e2442cabc533b (MD5) Previous issue date: 2013-02-18
In healthy women, a great number of intra and extracellular controls prevent the attachment and proliferation of ectopic endometrial cells. In endometriosis, abnormalities in those controls can lead to the survival of endometrial cells and consequently their attachment to the peritoneal cavity and disease progression. Endometrial cells with genetic polymorphisms respond to local signals, and they proliferate instead of undergoing apoptosis. The products of these abnormal cells stimulate the invasion of tissues and induce an inflammatory response. The disease has a complex trait and it is related to several factors such as genetic, immunological and environmental. This study examined six polymorphisms presented by six different genes (p53;
Estrogen Receptor β; Progesterone receptor; GSTM1; GSTT1; CYP1A1). We obtained the polymorphic genotype frequencies from the same 50 patients for all genes and we analyzed them using the Fisher's Exact Test or G Test. First we analyzed the genes in a group of two and subsequently in a group of three. We found significant association between polymorphisms in six pairs of genes (p53-Erβ with frequency 5.9 times higher in the experimental group; p53-GSTM1, 2.39 times higher; p53-CYP1A1 with 65.5% of the patients with the polymorphism; ERβ-PROGINS 3.0 times higher in the experimental group; GSTM1-PROGINS and GSTT1-CYP1A1 both with 31.25% of the patients with the polymorphism). Positive results were found in 15 situations when genes were analyzed in a group of three; the most significant result corresponding to the polymorphisms of the genes p53, Erβ e GSTM1 with 20% of the patients carrying these polymorphisms; PROGINS, Erβ e GSTM1 with 18%
and p53, Erβ e PROGINS with 12%. The results support the idea that the presence of polymorphisms in more than one endometriosis-related gene can lead to the onset of the disease and its progression. Studies should aim at these genes in order to understand the relationship among them more clearly and the possibility of developing new diagnostic techniques based on molecular markers of these genes.
Controles intra e extracelulares impedem a implantação e a proliferação de células endometriais ectópicas nas mulheres saudáveis. Anormalidades em quaisquer desses controles levam à sobrevida dessas células, implantação e a consequente progressão da Endometriose. Células endometriais com polimorfismos genéticos respondem a sinais locais e se proliferam não sofrendo apoptose. Os produtos dessas células anormais estimulam a invasão de tecidos e induzem respostas inflamatórias. A doença é complexa e relacionada a fatores como o genético, o imunológico e o ambiental. Este trabalho
analisou seis polimorfismos de seis diferentes genes (p53; Receptor β de estrógeno; Receptor de progesterona; GSTM1; GSTT1; CYP1A1).…
Advisors/Committee Members: Moura, Katia Karina Verolli de Oliveira.
Subjects/Keywords: Polimorfismo; p53; Receptor β; de estrógeno; Receptor de progesterona; GSTM1; GSTT1; CYP1A1; Endometriose; Polymorphism; p53; Estrogen Receptor β; Progesterone receptor; GSTM1; GSTT1; CYP1A1; Endometriosis; CNPQ::CIENCIAS BIOLOGICAS::GENETICA
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Silva, K. S. F. e. (2013). POLIMORFISMOS GENÉTICOS EM PACIENTES DE GOIÂNIA COM ENDOMETRIOSE: UM ESTUDO ANALÍTICO. (Masters Thesis). Pontifícia Universidade Católica de Goiás; Genética; PUC Goiás; BR; Ciências Humanas. Retrieved from http://localhost:8080/tede/handle/tede/2366
Chicago Manual of Style (16th Edition):
Silva, Kleber Santiago Freitas e. “POLIMORFISMOS GENÉTICOS EM PACIENTES DE GOIÂNIA COM ENDOMETRIOSE: UM ESTUDO ANALÍTICO.” 2013. Masters Thesis, Pontifícia Universidade Católica de Goiás; Genética; PUC Goiás; BR; Ciências Humanas. Accessed April 17, 2021.
http://localhost:8080/tede/handle/tede/2366.
MLA Handbook (7th Edition):
Silva, Kleber Santiago Freitas e. “POLIMORFISMOS GENÉTICOS EM PACIENTES DE GOIÂNIA COM ENDOMETRIOSE: UM ESTUDO ANALÍTICO.” 2013. Web. 17 Apr 2021.
Vancouver:
Silva KSFe. POLIMORFISMOS GENÉTICOS EM PACIENTES DE GOIÂNIA COM ENDOMETRIOSE: UM ESTUDO ANALÍTICO. [Internet] [Masters thesis]. Pontifícia Universidade Católica de Goiás; Genética; PUC Goiás; BR; Ciências Humanas; 2013. [cited 2021 Apr 17].
Available from: http://localhost:8080/tede/handle/tede/2366.
Council of Science Editors:
Silva KSFe. POLIMORFISMOS GENÉTICOS EM PACIENTES DE GOIÂNIA COM ENDOMETRIOSE: UM ESTUDO ANALÍTICO. [Masters Thesis]. Pontifícia Universidade Católica de Goiás; Genética; PUC Goiás; BR; Ciências Humanas; 2013. Available from: http://localhost:8080/tede/handle/tede/2366
UCLA
18.
Solaimani, Parrisa Sherry.
RNAi High Throughput Screenings Facilitate the Identification of Proteins Necessary for TCDD-induced CYP1A1 Enzymatic Activity and Aid in the Discovery of a Novel Role for Sin3A in AHR-Mediated Gene Expression.
Degree: Molecular Toxicology, 2012, UCLA
URL: http://www.escholarship.org/uc/item/39p7h68f
► The aryl hydrocarbon receptor (AHR) pathway is activated upon exposure to environmental pollutants 2,3,7,8-tetrachlorodibenzo-�-dioxin (TCDD) and benzo[a]pyrene (B[a]P), which leads to the induced expression of…
(more)
▼ The aryl hydrocarbon receptor (AHR) pathway is activated upon exposure to environmental pollutants 2,3,7,8-tetrachlorodibenzo-�-dioxin (TCDD) and benzo[a]pyrene (B[a]P), which leads to the induced expression of several genes. Toxicity of AHR occurs through the bioactivation of procarcinogens and eicosanoids by its target genes. In this study we identified several proteins that modulate the induction of the AHR target gene Cyp1a1. For this purpose we optimized procedures for the use of an RNAi high throughput screening, as well as for the construction and use of endoribonuclease-prepared siRNA (esiRNA) to validate the screening results. Expression of PDC, CD9, TMEM5, and Sin3A were found to be necessary for the induction of CYP1A1 whereas expression of Rbm5, ARMC8, PDC, CD9, TMEM5, Sin3A, Rab40C, Rad50, and Ube2i were necessary for both AHR expression and CYP1A1 induction. Additional studies were performed on the transcription factor candidate Sin3A, from which we found that Sin3A physically associates with the 5'-flanking regulatory regions of CYP1A1 in both human and mouse cell lines, and may potentially act as a coactivator for CYP1A1 induction. These studies established an essential role for Sin3A in the AHR-mediated induction of gene expression. We next examined the role of eicosanoids in AHR-dependent TCDD toxicity. CYP1A1, and other cytochrome P450s such as CYP2S1, can metabolize arachidonic acid into a variety of bioactive eicosanoids which play a significant role in the inflammatory response. From these studies we found that TCDD increased the levels of eicosanoids likely generated by cytochrome P450s in several tissues. Furthermore, these changes correlated with an increase in CYP1A1, CYP1B1, and CYP1A2 mRNA expression and were observed in wildtype mice but not AhR null mice. This demonstrated that these effects are mediated through AHR. Lastly, we explored dexamethasone-mediated regulation of CYP2S1. An initial screening looking for inhibitors of CYP2S1 revealed that dexamethasone, a glucocorticoid receptor (GR) ligand used to treat inflammatory diseases, represses its expression in multiple cell lines. We further found that dexamethasone regulates CYP2S1 via the GR and this occurs through the recruitment of histone deacetylases to the CYP2S1 promoter and enhancer.
Subjects/Keywords: Toxicology; Genetics; Molecular biology; AHR; CYP1A1; CYP2S1; Eicosanoids; High Throughput Screening; TCDD
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APA ·
Chicago ·
MLA ·
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CSE |
Export
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APA (6th Edition):
Solaimani, P. S. (2012). RNAi High Throughput Screenings Facilitate the Identification of Proteins Necessary for TCDD-induced CYP1A1 Enzymatic Activity and Aid in the Discovery of a Novel Role for Sin3A in AHR-Mediated Gene Expression. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/39p7h68f
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Solaimani, Parrisa Sherry. “RNAi High Throughput Screenings Facilitate the Identification of Proteins Necessary for TCDD-induced CYP1A1 Enzymatic Activity and Aid in the Discovery of a Novel Role for Sin3A in AHR-Mediated Gene Expression.” 2012. Thesis, UCLA. Accessed April 17, 2021.
http://www.escholarship.org/uc/item/39p7h68f.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Solaimani, Parrisa Sherry. “RNAi High Throughput Screenings Facilitate the Identification of Proteins Necessary for TCDD-induced CYP1A1 Enzymatic Activity and Aid in the Discovery of a Novel Role for Sin3A in AHR-Mediated Gene Expression.” 2012. Web. 17 Apr 2021.
Vancouver:
Solaimani PS. RNAi High Throughput Screenings Facilitate the Identification of Proteins Necessary for TCDD-induced CYP1A1 Enzymatic Activity and Aid in the Discovery of a Novel Role for Sin3A in AHR-Mediated Gene Expression. [Internet] [Thesis]. UCLA; 2012. [cited 2021 Apr 17].
Available from: http://www.escholarship.org/uc/item/39p7h68f.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Solaimani PS. RNAi High Throughput Screenings Facilitate the Identification of Proteins Necessary for TCDD-induced CYP1A1 Enzymatic Activity and Aid in the Discovery of a Novel Role for Sin3A in AHR-Mediated Gene Expression. [Thesis]. UCLA; 2012. Available from: http://www.escholarship.org/uc/item/39p7h68f
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Alberta
19.
Anwar-Mohamed, Anwar Gamal Abd El-Naser.
MODULATION OF ARYL HYDROCARBON RECEPTOR (AHR)-REGULATED
XENOBIOTIC METABOLIZING ENZYMES BY ARSENITE.
Degree: PhD, Faculty of Pharmacy and Pharmaceutical
Sciences, 2013, University of Alberta
URL: https://era.library.ualberta.ca/files/1r66j218m
► Aryl hydrocarbon receptor (AhR) ligands and heavy metals are environmental co-contaminants and their molecular interaction may disrupt the coordinated regulation of AhR-dependent phase I and…
(more)
▼ Aryl hydrocarbon receptor (AhR) ligands and heavy
metals are environmental co-contaminants and their molecular
interaction may disrupt the coordinated regulation of AhR-dependent
phase I and II drug metabolizing enzymes. As such, the effect of
the heavy metal, As(III), on the AhR-regulated genes cytochrome
P450 1A1 (CYP1A1), CYP1A2, CYP1B1, NAD(P)H: quinone oxidoreductase
(NQO1), and glutathione S-transferase a1 subunit (GSTA1) was
investigated. In HepG2 cells, As(III) significantly inhibited
CYP1A1 at the mRNA, protein, and catalytic activity levels in a
concentration- and time-dependent manner. As(III) significantly
increased heme oxygenase-1 (HO-1), which coincided with a decrease
in the CYP1A1 catalytic activity levels. The use of an HO-1
inhibitor, tin mesoporphyrin, a heme precursor, hemin, or
transfecting the HepG2 cells with siRNA against HO-1 partially
reversed the As(III)-mediated inhibition of the TCDD-mediated
induction of CYP1A1 catalytic activity. Similarly, in rat primary
hepatocytes, As(III) decreased CYP1A1, CYP1A2, CYP3A23, and CYP3A2
expression, and inhibiting As(III)-mediated induction of HO-1
partially restored the enzymatic activity of these P450s. In
C57Bl/6 mice, As(III) modulated the constitutive and TCDD-induced
AhR-regulated genes in a time-, tissue-, and AhR-regulated
enzyme-specific manner. Additionally, As(III) increased the serum
hemoglobin (Hb) levels in animals treated for 24h, and upon
treatment of mouse isolated hepatocytes with Hb alone, there was an
increase in the nuclear accumulation of AhR and AhR-dependent
luciferase activity. Furthermore, Hb potentiated the TCDD-induced
AhR-dependent luciferase activity, implicating Hb as an in
vivo-specific modulator. Investigating the possible role of As(III)
metabolites as an alternative modulator to CYP1A1, we found that
methylated pentavalent arsenic metabolites are bifunctional
inducers as they increase CYP1A1 through activating the AhR/XRE
signaling pathway and they increase NQO1 through activating the
Nrf2/ARE signaling pathway in addition to the AhR/XRE pathway.
Future studies are required to determine the exact role of AhR-and
Nrf-2-regulated genes in the initiation and progression of
malignancies.
Subjects/Keywords: Cytochrome P450s; Drug Metabolizing Enzymes; Hepatocytes; Liver; Arsenic metabolites; CYP1A1; Aryl Hydrocarbon Receptor; Arsenite
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APA ·
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APA (6th Edition):
Anwar-Mohamed, A. G. A. E. (2013). MODULATION OF ARYL HYDROCARBON RECEPTOR (AHR)-REGULATED
XENOBIOTIC METABOLIZING ENZYMES BY ARSENITE. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/1r66j218m
Chicago Manual of Style (16th Edition):
Anwar-Mohamed, Anwar Gamal Abd El-Naser. “MODULATION OF ARYL HYDROCARBON RECEPTOR (AHR)-REGULATED
XENOBIOTIC METABOLIZING ENZYMES BY ARSENITE.” 2013. Doctoral Dissertation, University of Alberta. Accessed April 17, 2021.
https://era.library.ualberta.ca/files/1r66j218m.
MLA Handbook (7th Edition):
Anwar-Mohamed, Anwar Gamal Abd El-Naser. “MODULATION OF ARYL HYDROCARBON RECEPTOR (AHR)-REGULATED
XENOBIOTIC METABOLIZING ENZYMES BY ARSENITE.” 2013. Web. 17 Apr 2021.
Vancouver:
Anwar-Mohamed AGAE. MODULATION OF ARYL HYDROCARBON RECEPTOR (AHR)-REGULATED
XENOBIOTIC METABOLIZING ENZYMES BY ARSENITE. [Internet] [Doctoral dissertation]. University of Alberta; 2013. [cited 2021 Apr 17].
Available from: https://era.library.ualberta.ca/files/1r66j218m.
Council of Science Editors:
Anwar-Mohamed AGAE. MODULATION OF ARYL HYDROCARBON RECEPTOR (AHR)-REGULATED
XENOBIOTIC METABOLIZING ENZYMES BY ARSENITE. [Doctoral Dissertation]. University of Alberta; 2013. Available from: https://era.library.ualberta.ca/files/1r66j218m
20.
Κουμαντάκης, Γεώργιος.
Ανίχνευση συχνοτήτων πολυμορφισμών και παρουσίας των γονιδίων CYP1A1, GSTM1, GSTT και CYP19A1 σε γυναίκες με ενδομητρίωση.
Degree: 2006, University of Crete (UOC); Πανεπιστήμιο Κρήτης
URL: http://hdl.handle.net/10442/hedi/16116
Subjects/Keywords: Ενδομητρίωση; Endometriosis; CYP1A1; CYP19; GSTM1; GSTT
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APA ·
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APA (6th Edition):
Κουμαντάκης, . . (2006). Ανίχνευση συχνοτήτων πολυμορφισμών και παρουσίας των γονιδίων CYP1A1, GSTM1, GSTT και CYP19A1 σε γυναίκες με ενδομητρίωση. (Thesis). University of Crete (UOC); Πανεπιστήμιο Κρήτης. Retrieved from http://hdl.handle.net/10442/hedi/16116
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Κουμαντάκης, Γεώργιος. “Ανίχνευση συχνοτήτων πολυμορφισμών και παρουσίας των γονιδίων CYP1A1, GSTM1, GSTT και CYP19A1 σε γυναίκες με ενδομητρίωση.” 2006. Thesis, University of Crete (UOC); Πανεπιστήμιο Κρήτης. Accessed April 17, 2021.
http://hdl.handle.net/10442/hedi/16116.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Κουμαντάκης, Γεώργιος. “Ανίχνευση συχνοτήτων πολυμορφισμών και παρουσίας των γονιδίων CYP1A1, GSTM1, GSTT και CYP19A1 σε γυναίκες με ενδομητρίωση.” 2006. Web. 17 Apr 2021.
Vancouver:
Κουμαντάκης . Ανίχνευση συχνοτήτων πολυμορφισμών και παρουσίας των γονιδίων CYP1A1, GSTM1, GSTT και CYP19A1 σε γυναίκες με ενδομητρίωση. [Internet] [Thesis]. University of Crete (UOC); Πανεπιστήμιο Κρήτης; 2006. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/10442/hedi/16116.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Κουμαντάκης . Ανίχνευση συχνοτήτων πολυμορφισμών και παρουσίας των γονιδίων CYP1A1, GSTM1, GSTT και CYP19A1 σε γυναίκες με ενδομητρίωση. [Thesis]. University of Crete (UOC); Πανεπιστήμιο Κρήτης; 2006. Available from: http://hdl.handle.net/10442/hedi/16116
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
21.
Chamelete, André [UNESP].
Avaliação da expressão dos genes cFOS, IL-1b, CYP1a1 e CYP1b1 em Danio rerio expostos a Benzo[a]pireno e tratados com ligantes do receptor P2X7.
Degree: 2016, Universidade Estadual Paulista (UNESP)
URL: http://hdl.handle.net/11449/134243
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Made available in DSpace on 2016-02-12T17:20:57Z (GMT). No. of bitstreams: 1 chamelete_a_me_sjrp.pdf: 663322 bytes, checksum: 5ca648d67a3a798d08f9c68653ac3ca2 (MD5) Previous issue date: 2016-01-25
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
O BaP é um contaminante ambiental capaz de causar inflamação e desregulação de vias celulares. Pela ação da CYP1a1 e CYP1b1, é convertido a metabólitos mais reativos. A literatura mostra que o BaP aumenta a expressão de algumas citocinas
próinflamatórias, como a IL-1, porém, são bem contraditórios os relatos sobre o efeito do BaP no cFOS, o qual apresenta papel importante na proliferação, na formação de tumores e, possivelmente, na inflamação. O objetivo deste estudo foi de elucidar a participação do receptor purinérgico P2X7 sobre a expressão dos genes IL-1 e cFOS, durante exposição ao BaP. Foi empregado as técnicas de qPCR para quantificação de expressão gênica, e testes de correlação e regressão entre IL-1 e cFOS. A exposição ao BaP induziu a expressão dos dois genes, além das enzimas do seu metabolismo. Quando bloqueado o receptor P2X7, além de uma menor indução das CYPs, os níveis de IL-1 e cFOS caíram abaixo dos níveis controle, sugerindo a participação do P2X7. Os testes de correlação e regressão mostraram uma relação forte direta entre IL-1 e cFOS, reforçando o papel do cFOS na inflamação.
BaP is an environmental contaminant capable to cause inflammation and impair cellular pathways. CYP1a1 and CYP1b1
convert it to more reactive metabolites. Studies show that BaP enhances some proinflammatory citokines expression, like IL-1, yet reports about BaP affecting cFOS, which plays important role in proliferation, tumor formation and inflammation, are controversial. This work aimed to elucidate whether P2X7 purinergic receptor plays a role in IL-1 and cFOS expression during BaP exposure. We applied qPCR techniques to quantify gene expression, correlation and regression assays. Our results showed that BaP raised both IL-1 and cFOS genes expression, besides CYPs ones. Morevoer, when blocking P2X7 receptor, IL-1 and cFOS expression dropped under normal levels, which suggest P2X7 participation, in addition to a smaller enzymes induction. Correlation and regression assays exhibited a strong straight relationship between IL-1 and cFOS expression, reinforcing the role of cFOS in inflammation.
Advisors/Committee Members: Universidade Estadual Paulista (UNESP), Campos, Marcelo [UNESP].
Subjects/Keywords: cFOS; CYP1a1; CYP1b1; Danio rerio; P2x7; Benzo[a]pireno; Benzo[a]pyrene
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APA (6th Edition):
Chamelete, A. [. (2016). Avaliação da expressão dos genes cFOS, IL-1b, CYP1a1 e CYP1b1 em Danio rerio expostos a Benzo[a]pireno e tratados com ligantes do receptor P2X7. (Masters Thesis). Universidade Estadual Paulista (UNESP). Retrieved from http://hdl.handle.net/11449/134243
Chicago Manual of Style (16th Edition):
Chamelete, André [UNESP]. “Avaliação da expressão dos genes cFOS, IL-1b, CYP1a1 e CYP1b1 em Danio rerio expostos a Benzo[a]pireno e tratados com ligantes do receptor P2X7.” 2016. Masters Thesis, Universidade Estadual Paulista (UNESP). Accessed April 17, 2021.
http://hdl.handle.net/11449/134243.
MLA Handbook (7th Edition):
Chamelete, André [UNESP]. “Avaliação da expressão dos genes cFOS, IL-1b, CYP1a1 e CYP1b1 em Danio rerio expostos a Benzo[a]pireno e tratados com ligantes do receptor P2X7.” 2016. Web. 17 Apr 2021.
Vancouver:
Chamelete A[. Avaliação da expressão dos genes cFOS, IL-1b, CYP1a1 e CYP1b1 em Danio rerio expostos a Benzo[a]pireno e tratados com ligantes do receptor P2X7. [Internet] [Masters thesis]. Universidade Estadual Paulista (UNESP); 2016. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/11449/134243.
Council of Science Editors:
Chamelete A[. Avaliação da expressão dos genes cFOS, IL-1b, CYP1a1 e CYP1b1 em Danio rerio expostos a Benzo[a]pireno e tratados com ligantes do receptor P2X7. [Masters Thesis]. Universidade Estadual Paulista (UNESP); 2016. Available from: http://hdl.handle.net/11449/134243
Freie Universität Berlin
22.
Thomae, Michael.
Polymorphic variants of Cytochrome P450 1A1 and colorectal cancer
susceptibility.
Degree: 2010, Freie Universität Berlin
URL: http://dx.doi.org/10.17169/refubium-4963
► The development of colorectal carcinoma is strongly influenced by environmental factors. Cytochrome P 450 1A1 (CYP1A1) plays a key role in chemical carcinogenesis by activating…
(more)
▼ The development of colorectal carcinoma is strongly influenced by
environmental factors. Cytochrome P 450 1A1 (
CYP1A1) plays a key role in
chemical carcinogenesis by activating carcinogenic substances like polycyclic
aromatic hydrocarbons. This study compares the frequencies of seven
polymorphic variants of CYP 4501A1 (v1-v7) in colorectal cancer patients and
in control patients and analyses, whether carriers of definite variants are at
a higher cancer risk. Additionally, we analysed the role of
CYP1A1 variants as
risk factors in relation to tobacco use. To assess dose effects, we contrasted
non-smokers with smokers with 1-39 pack-years of smoking (RI, n=48), smokers
with 39-59 pack-years of smoking (RII, n=26), and smokers with more than 59
pack-years of smoking (RIII, n=22). We examined a total of 285 colorectal
carcinoma patients of Russian origin and 270 healthy individuals. Subjects
were genotyped for seven single nucleotide polymorphisms (v1, v2, v3, v4, v5,
v6, v7) using PCR-RLFP. These SNPs are allocated to the alleles *H0, *2A, *2B,
*3, *4, *1D, *1E. The
CYP1A1*1D allele was underrepresented in the colorectal
carcinoma group (p=0.02), *1E was overrepresented in the smoker group RI
(p=0.05). Genotype analysis revealed that H0/H0 (homozygote wildtype) was
overrepresented in colorectal carcinoma patients (OR 1.42; 95% CI (1.1-1.8),
p=0.006) whereas the genotype H0/*1D was underrepresented in this group (0.72;
95% CI (0.58-0.89), p=0.03). The protective effect of the homozygote genotype
*1D/*1D was even stronger (OR 0.54; 95% CI (0.32-0.93, p=0,03)). A significant
reduction of colorectal carcinoma risk was found for carriers of the *1D-
allele (OR 0,69; 95% CI 0,55-0,87, p=0,001). The smoker sub-group analysis
identified the genotypes H0/*1E (p=0.03) and H0/*2A (p=0.05) as
overrepresented in the smoker group RI. These findings suggest that genetic
variants of
CYP1A1 modify the risk of colorectal cancer. Carriers of the
allele *1D are at a reduced risk for colorectal carcinoma, whereas smokers
carrying the genotypes H0/*2A and H0/*1E seem to be at a higher risk.
Advisors/Committee Members: m (gender), Prof. Dr. med. I. Roots (firstReferee), Prof. Dr. med. J. Brockmöller, PD Dr. med. H.-D. Orzechowski (furtherReferee).
Subjects/Keywords: cytochrome P-450-polymorphisms; cyp1a1; colorectal cancer susceptibility; 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Thomae, M. (2010). Polymorphic variants of Cytochrome P450 1A1 and colorectal cancer
susceptibility. (Thesis). Freie Universität Berlin. Retrieved from http://dx.doi.org/10.17169/refubium-4963
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Thomae, Michael. “Polymorphic variants of Cytochrome P450 1A1 and colorectal cancer
susceptibility.” 2010. Thesis, Freie Universität Berlin. Accessed April 17, 2021.
http://dx.doi.org/10.17169/refubium-4963.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Thomae, Michael. “Polymorphic variants of Cytochrome P450 1A1 and colorectal cancer
susceptibility.” 2010. Web. 17 Apr 2021.
Vancouver:
Thomae M. Polymorphic variants of Cytochrome P450 1A1 and colorectal cancer
susceptibility. [Internet] [Thesis]. Freie Universität Berlin; 2010. [cited 2021 Apr 17].
Available from: http://dx.doi.org/10.17169/refubium-4963.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Thomae M. Polymorphic variants of Cytochrome P450 1A1 and colorectal cancer
susceptibility. [Thesis]. Freie Universität Berlin; 2010. Available from: http://dx.doi.org/10.17169/refubium-4963
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Freie Universität Berlin
23.
Keyserling, Helmut Graf von.
Real time PCR-based diagnostic and prognostic assays for the early detection
of cervical cancer.
Degree: 2012, Freie Universität Berlin
URL: http://dx.doi.org/10.17169/refubium-11981
► The aim of this study was to evaluate different diagnostic and prognostic biomarkers with respect to their feasibility in cervical cancer diagnosis using real-time PCR…
(more)
▼ The aim of this study was to evaluate different diagnostic and prognostic
biomarkers with respect to their feasibility in cervical cancer diagnosis
using real-time PCR protocols. First we analysed different mRNA based
diagnostic markers in a standard clinical setting. Particularly we explored
the transcripts p14ARF and p16INK4A regarding to their usability in cancer
screening. Higher levels of these mRNAs may indicate HPV type-independently
the up regulation of E6 and E7 oncogene expression that in turn indicates
malignant transformation. Additionally we analysed the influence of age on the
expression of p14ARF and p16INK4A. The p14ARF and p16INK4A expression levels
relative to the housekeeping gene ACTB were significantly up- regulated in
HSIL patients. A significant age-related bias was observed. Our results
support wariness in interpretation of p14ARF and p16INK4A mRNA expression
results from older patients. Additionally, we analysed different single
nucleotide polymorphisms (SNPs) regarding to their prognostic usability
because genetic epidemiological studies showed that SNPs contribute to disease
risk. We developed a platform procedure to analyse such genetic risk factors
retrospectively using patient material that accumulates in many gynecologic
laboratories. We applied a new approach that is inferencing by semantic
integration the different clinical diagnoses and is assigning a severity index
for each patient. Also a multiplex ligation-dependent polymerase chain
reaction approach was designed for SNP analysis using low-input concentration
genomic DNA. We have chosen a set of SNPs in genes that are involved in
deregulation of cell cycle proteins, genetic repair mechanisms, and cell
detoxification because they may contribute to disease progression. This study
revealed genetic associations of a rare SNP genotype with cervical dysplasia
in one of the largest patient sample to date and warrants further
investigation. The severity index data were also used to analyse the effect of
deletions in glutathion-S transferases. Here we applied a multiplex PCR assay
with melting curve read out and particularly analysed for gene–environment
interactions. From these melting curve data we could derive a method for
temperature validation of real-time PCR instruments. By ap¬plying high-
resolution melting (HRM) analysis using a defined PCR amplicon and EvaGreen
dye, information about the temperature accuracy and thermal homogeneity of the
heating block was obtained. The advantages of this HRM-based method include i)
temperature measurement under real world conditions in the reaction liquid in
closed reaction tubes; ii) temperature measurement of all wells; iii) and
applica¬bility to all real-time PCR instruments capable of HRM analysis.
Advisors/Committee Members: m (gender), PD Dr. Andreas M. Kaufmann (firstReferee), PD Dr. Ingeborg Zehbe (furtherReferee), Prof. Dr. Peter Öhlschläger (furtherReferee).
Subjects/Keywords: cervical cancer; P16ink4a; CYP1A1; "real-time PCR"; 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Keyserling, H. G. v. (2012). Real time PCR-based diagnostic and prognostic assays for the early detection
of cervical cancer. (Thesis). Freie Universität Berlin. Retrieved from http://dx.doi.org/10.17169/refubium-11981
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Keyserling, Helmut Graf von. “Real time PCR-based diagnostic and prognostic assays for the early detection
of cervical cancer.” 2012. Thesis, Freie Universität Berlin. Accessed April 17, 2021.
http://dx.doi.org/10.17169/refubium-11981.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Keyserling, Helmut Graf von. “Real time PCR-based diagnostic and prognostic assays for the early detection
of cervical cancer.” 2012. Web. 17 Apr 2021.
Vancouver:
Keyserling HGv. Real time PCR-based diagnostic and prognostic assays for the early detection
of cervical cancer. [Internet] [Thesis]. Freie Universität Berlin; 2012. [cited 2021 Apr 17].
Available from: http://dx.doi.org/10.17169/refubium-11981.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Keyserling HGv. Real time PCR-based diagnostic and prognostic assays for the early detection
of cervical cancer. [Thesis]. Freie Universität Berlin; 2012. Available from: http://dx.doi.org/10.17169/refubium-11981
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Bradford
24.
Alandas, Mohammed Nasser.
An investigation into the metabolic activation of novel chloromethylindolines by isoforms of cytochrome P450 : targeting drug metabolising enzymes in cancer : analysis of the role and function of selected cytochrome P450 oxidising novel cancer prodrugs.
Degree: PhD, 2012, University of Bradford
URL: http://hdl.handle.net/10454/6289
► Introduction: Cytochromes P450 (CYPs) are the major family of enzymes responsible for detoxification and metabolism of a wide range of both endogenous and xenobiotics chemicals…
(more)
▼ Introduction: Cytochromes P450 (CYPs) are the major family of enzymes responsible for detoxification and metabolism of a wide range of both endogenous and xenobiotics chemicals in living organisms. The use of CYPs to activate prodrugs to cytotoxins selectively in tumours has been explored including AQ4N, Phortress and Aminoflavone. CYP1A1, CYP1B1, CYP2W1, and CYP4F11 have been identified as expressed in tumour tissue and surrounding stroma at high frequency compared to most normal tissues. Aim is to investigate the differential metabolism of novel chloromethylindoline by high frequency expressed CYPs in tumours. This differential may be exploited to elicit a selective chemotherapeutic effect by metabolising inert small molecules to potent cytotoxins within the tumour environment. Materials and Methods: Sensitive and specific LC/MS/MS techniques have been developed to investigate the metabolism of chloromethylindolines. Recombinant enzymes and transfected cell lines were used to investigate the metabolic profiles with a focus on production of the cytotoxic derivatives of chloromethylindolines. Results: Detailed metabolic studies show that (1-(Chloromethyl)-1,2-dihydropyrrolo [3,2-e]indol-3(6H)-yl)(5-methoxy-1H-indol-2-yl) methanone (ICT2700) and other chloromethylindolines are converted by CYP1A1 mediated hydroxylation at the C-5 position leading to highly potent metabolites. In vitro cytotoxicity studies showed differentials of up to 1000-fold was achieved between CYP1A1 activated compared to the non-metabolised parent molecules. The reactivity of metabolites of ICT2700 was also explored using glutathione as a nucleophile. The metabolites were identified by a combination of LC/MS and LC MS/MS techniques. Investigations using mouse and human liver microsomes show that a large number of metabolites are created though none were shown to be associated with a potential anticancer effect. Studies focused on CYP2W1 show that this isoform metabolised ICT2706 to a cytotoxic species and a pharmacokinetic study showed a good distribution of ICT2706 into mouse tissues including tumour. However metabolism of ICT2726 by CYP2W1 resulted only in a non-toxic metabolite profile and may have potential as a biomarker for functional CYP2W1 in tissues. Preliminary studies show that palmitic acid hydroxylation is a useful marker of functional CYP4F11. Summary and conclusion: The in vitro results show that the chloromethylindolines are a novel class of agent with potential as prodrugs that following specific hydroxylation by CYP1A1 and CYP2W1 are converted to ultra-potent cytotoxins. Other metabolites are also evident which are not cytotoxic. Studies in vivo show that selected chloromethylindolines possess a good pharmacokinetic profile and show potential as prodrug anticancer agents that require activation by CYP1A1 or CYP2W1. The methods, results, progress and suggestions for future work are presented in this thesis.
Subjects/Keywords: 616.99; Cancer; Pharmacokinetics; Drug metabolism; Chloromethylindolines; CYP1A1, CYP2W1, CYP4F11; Microsomes; Cytotoxic; LC-MS/MS; Cytochromes P450; Prodrugs
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Alandas, M. N. (2012). An investigation into the metabolic activation of novel chloromethylindolines by isoforms of cytochrome P450 : targeting drug metabolising enzymes in cancer : analysis of the role and function of selected cytochrome P450 oxidising novel cancer prodrugs. (Doctoral Dissertation). University of Bradford. Retrieved from http://hdl.handle.net/10454/6289
Chicago Manual of Style (16th Edition):
Alandas, Mohammed Nasser. “An investigation into the metabolic activation of novel chloromethylindolines by isoforms of cytochrome P450 : targeting drug metabolising enzymes in cancer : analysis of the role and function of selected cytochrome P450 oxidising novel cancer prodrugs.” 2012. Doctoral Dissertation, University of Bradford. Accessed April 17, 2021.
http://hdl.handle.net/10454/6289.
MLA Handbook (7th Edition):
Alandas, Mohammed Nasser. “An investigation into the metabolic activation of novel chloromethylindolines by isoforms of cytochrome P450 : targeting drug metabolising enzymes in cancer : analysis of the role and function of selected cytochrome P450 oxidising novel cancer prodrugs.” 2012. Web. 17 Apr 2021.
Vancouver:
Alandas MN. An investigation into the metabolic activation of novel chloromethylindolines by isoforms of cytochrome P450 : targeting drug metabolising enzymes in cancer : analysis of the role and function of selected cytochrome P450 oxidising novel cancer prodrugs. [Internet] [Doctoral dissertation]. University of Bradford; 2012. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/10454/6289.
Council of Science Editors:
Alandas MN. An investigation into the metabolic activation of novel chloromethylindolines by isoforms of cytochrome P450 : targeting drug metabolising enzymes in cancer : analysis of the role and function of selected cytochrome P450 oxidising novel cancer prodrugs. [Doctoral Dissertation]. University of Bradford; 2012. Available from: http://hdl.handle.net/10454/6289
University of Georgia
25.
McPhail, Brooks Tia'.
The ontogeny of cytochrome P450 (CYP450) activity, expression and volatile organic compound (VOC) metabolism in Sprague-Dawley (S-D) rats.
Degree: 2014, University of Georgia
URL: http://hdl.handle.net/10724/25000
► CYP450 levels are altered by development and minimum metabolism occurs in the young due to an under developed hepatic system. A minimum amount of data…
(more)
▼ CYP450 levels are altered by development and minimum metabolism occurs in the young due to an under developed hepatic system. A minimum amount of data is available for developmental toxicological studies. Rodents are often used as surrogates
for toxicological and pharmaceutical studies. In the current study, Sprague-Dawley (S-D) rats were used to assess the enzymatic activity, protein expression and metabolic capabilities of developing post-natal day (PND) rodents. Cytochrome P450 (CYP450)
enzymes are members of Phase I metabolism which are involved in the oxidation, reduction and hydrolysis of compounds. CYP2E1, CYP1A1/2 and CYP2B1/2 are the predominate isozymes responsible for the metabolism of xenobiotics. PNDs 1, 5, 10, 15, 21, 30, 40,
50, 60 and 90 hepatic microsomes were used to measure the ontogeny of each isozyme enzymatic activity and protein expression. CYP2E1 activity and expression showed a decrease with an increase in age, with peak levels occurring at PND 21; CYP1A1/2 showed
slightly lower activity and expression in younger animals with peak levels occurring between PND 21 through 40; CYP2B1/2 activity and expression was also slightly lower in younger animals with peak levels occurring at PND 21. After the enzymatic activity
and protein expression was established, the metabolic capacity of PND 10, 15, 21, 60 and 90 were determined using the Michaelis-Menten parameters Km and Vmax in hepatic microsomal samples. The volatile organic compounds (VOCs) dichloromethane (DCM),
trichloroethylene (TCE) and perchloroethylene (PERC) were used to measure the hepatic microsomal metabolism. Each VOC is commonly used in industrial settings and are metabolized by Phase I CYP450s. DCM, TCE and PERC showed an increase in metabolism with
an increase in time and protein concentration. Although TCE and PERC are high and low metabolizing compounds, respectively, which form similar metabolites, DCM and TCE metabolism showed a similar pattern throughout development while PERC remained
relatively constant. In spite of these differences, each compound showed peak Vmax levels at PND 21. The current study has shown that rodents have the highest enzymatic activity, protein expression and metabolic ability prior to adulthood; therefore,
this data could prove useful in the risk assessment of VOCs for developing humans.
Subjects/Keywords: Cytochrome P450 (CYP450); CYP2E1; CYP1A1/2; CYP2B1/2; Sprague-Dawley rats; Dichloromethane (DCM); Trichloroethylene (TCE); Perchloroethylene (PERC); Michaelis-Menten; Vmax; Km
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
McPhail, B. T. (2014). The ontogeny of cytochrome P450 (CYP450) activity, expression and volatile organic compound (VOC) metabolism in Sprague-Dawley (S-D) rats. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/25000
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
McPhail, Brooks Tia'. “The ontogeny of cytochrome P450 (CYP450) activity, expression and volatile organic compound (VOC) metabolism in Sprague-Dawley (S-D) rats.” 2014. Thesis, University of Georgia. Accessed April 17, 2021.
http://hdl.handle.net/10724/25000.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
McPhail, Brooks Tia'. “The ontogeny of cytochrome P450 (CYP450) activity, expression and volatile organic compound (VOC) metabolism in Sprague-Dawley (S-D) rats.” 2014. Web. 17 Apr 2021.
Vancouver:
McPhail BT. The ontogeny of cytochrome P450 (CYP450) activity, expression and volatile organic compound (VOC) metabolism in Sprague-Dawley (S-D) rats. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/10724/25000.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
McPhail BT. The ontogeny of cytochrome P450 (CYP450) activity, expression and volatile organic compound (VOC) metabolism in Sprague-Dawley (S-D) rats. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/25000
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Cincinnati
26.
Dong, Hongbin.
Knock-in Mouse Lines Expressing Microsomal or Mitochondrial
CYP1A1: Variations in Response to Oral Benzo[a]pyrene.
Degree: PhD, Medicine : Toxicology (Environmental
Health), 2009, University of Cincinnati
URL: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1245449157
► In the past, CYP1A1 protein was known to be located in the endoplasmic reticulum (ER; microsomes). More recently, CYP1A1 was shown as well to be…
(more)
▼ In the past,
CYP1A1 protein was known to be located in
the endoplasmic reticulum (ER; microsomes). More recently,
CYP1A1
was shown as well to be targeted to the inner mitochondrial
membrane; mitochondrial import is dependent on NH2-terminal
processing that exposes cryptic targeting signals. It is
interesting that microsomal and mitochondrial
CYP1A1 enzymes
exhibit different electron donors, substrate specificities, and
inducer properties. To understand the physiological and
toxicological functions of microsomal versus mitochondrial
CYP1A1,
we generated three knock-in mouse lines by modifying the
CYP1A1
NH2-terminal signal sequence. <i>
Cyp1a1(mtt/mtt)</i>
mice encode an NH2-terminal 31-amino acid truncated protein,
deleting the entire ER-targeting signal domain and exposing the
cryptic mitochondrial-targeting signal.
<i>
Cyp1a1(mtp/mtp)</i> mice encode a protein carrying
L7N and L17N mutations; this mutant lacks the signal recognition
particle (SRP)-binding site and subsequent ER-targeting, but
requires cytosolic proteolysis for mitochondrial import.
<i>
Cyp1a1(mc/mc)</i> mice encode a microsomal protein
having R34D and K39I mutations, which abolish the
mitochondrial-targeting signals. After dioxin or
beta-naphthoflavone treatment of these mouse lines, the
CYP1A1
protein was shown to be located in the mitochondria of the
<i>
Cyp1a1(mtp/mtp)</i> and
<i>
Cyp1a1(mtt/mtt)</i> lines and in microsomes of the
<i>
Cyp1a1(mc/mc)</i> line. To test for differences in
function, we compared the response to dietary benzo[a]pyrene (BaP).
After 18 days of daily oral BaP treament, wild type and
<i>
Cyp1a1(mc/mc)</i> mice were completely protected,
whereas <i>
Cyp1a1(-/-)</i> and
<i>
Cyp1a1(mtp/mtp)</i> mice showed striking toxicity
and compensatory up-regulation of CYP1A2 and CYP1B1 mRNA in several
tissues. Our data support the likelihood that it is the microsomal
rather than mitochondrial
CYP1A1 enzyme that protects against
dietary BaP toxicity. Such variation in functions of subcellular
CYP1A1 isoforms may also exist under physiological conditions,
given that these isoforms have distinct enzymatic properties in
metabolizing endogenous substrates.
Advisors/Committee Members: Nebert, Daniel (Committee Chair).
Subjects/Keywords: Toxicology; CYP1A1; mice; BaP; mtp/mtp; MT1A1; Avadhani
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APA (6th Edition):
Dong, H. (2009). Knock-in Mouse Lines Expressing Microsomal or Mitochondrial
CYP1A1: Variations in Response to Oral Benzo[a]pyrene. (Doctoral Dissertation). University of Cincinnati. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=ucin1245449157
Chicago Manual of Style (16th Edition):
Dong, Hongbin. “Knock-in Mouse Lines Expressing Microsomal or Mitochondrial
CYP1A1: Variations in Response to Oral Benzo[a]pyrene.” 2009. Doctoral Dissertation, University of Cincinnati. Accessed April 17, 2021.
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1245449157.
MLA Handbook (7th Edition):
Dong, Hongbin. “Knock-in Mouse Lines Expressing Microsomal or Mitochondrial
CYP1A1: Variations in Response to Oral Benzo[a]pyrene.” 2009. Web. 17 Apr 2021.
Vancouver:
Dong H. Knock-in Mouse Lines Expressing Microsomal or Mitochondrial
CYP1A1: Variations in Response to Oral Benzo[a]pyrene. [Internet] [Doctoral dissertation]. University of Cincinnati; 2009. [cited 2021 Apr 17].
Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1245449157.
Council of Science Editors:
Dong H. Knock-in Mouse Lines Expressing Microsomal or Mitochondrial
CYP1A1: Variations in Response to Oral Benzo[a]pyrene. [Doctoral Dissertation]. University of Cincinnati; 2009. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1245449157
Wright State University
27.
Wourms, Michael J.
The Aryl Hydrocarbon Receptor Regulates an Essential
Transcriptional Element in the Immunoglobulin Heavy Chain
Gene.
Degree: MS, Pharmacology and Toxicology, 2013, Wright State University
URL: http://rave.ohiolink.edu/etdc/view?acc_num=wright1389551618
► 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant that inhibits immunoglobulin (Ig) expression and Ig heavy (IgH) chain gene transcription. Transcription of the IgH gene involves…
(more)
▼ 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a
ubiquitous environmental contaminant that inhibits immunoglobulin
(Ig) expression and Ig heavy (IgH) chain gene transcription.
Transcription of the IgH gene involves several regulatory elements
including the 3'<i>lgh</i> regulatory region
(3'<i>lgh</i>RR) which is composed of four enhancers
(hs3A, hs1,2, hs4, and hs3B). Dioxin responsive elements (DRE) in
the hs4 and hs1,2 enhancers of the 3<i>lgh</i>RR that
bind the aryl hydrocarbon receptor (AhR), a ligand-activated
transcription factor that regulates dioxin sensitive genes suggest
that the 3'<i>lgh</i>RR may be a transcriptional target
of TCDD. The current study utilized an IgA secreting mouse B-cell
line that stably expresses a γ 2b transgene regulated by the
3'<i>lgh</i>RR (CH12.γ 2b-3'<i>lgh</i>RR
cells). Both shRNA knock down of AhR and an AhR antagonist
(CH-223191) reduced TCDD-induced inhibition of endogenous IgA and
the γ 2b transgene expression. With the growing number of
immune-related disorders correlated with polymorphisms of the human
hs1,2 enhancer, ubiquitously found AhR ligands, and sensitivity of
human Ig expression to TCDD, our findings may provide indispensible
information for human health risk assessment and insight into the
development of therapeutic interventions for immune-related
disease.
Advisors/Committee Members: Sulentic, Courtney (Committee Chair).
Subjects/Keywords: Immunology; Pharmacology; Toxicology; aryl hydrocarbon receptor; AhR; immune deficient; autoimmunity; TCDD; dioxin; ARNT; immunoglobulin regulatory region; immunoglobulin heavy chain; Cyp1A1
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APA ·
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MLA ·
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Manager
APA (6th Edition):
Wourms, M. J. (2013). The Aryl Hydrocarbon Receptor Regulates an Essential
Transcriptional Element in the Immunoglobulin Heavy Chain
Gene. (Masters Thesis). Wright State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=wright1389551618
Chicago Manual of Style (16th Edition):
Wourms, Michael J. “The Aryl Hydrocarbon Receptor Regulates an Essential
Transcriptional Element in the Immunoglobulin Heavy Chain
Gene.” 2013. Masters Thesis, Wright State University. Accessed April 17, 2021.
http://rave.ohiolink.edu/etdc/view?acc_num=wright1389551618.
MLA Handbook (7th Edition):
Wourms, Michael J. “The Aryl Hydrocarbon Receptor Regulates an Essential
Transcriptional Element in the Immunoglobulin Heavy Chain
Gene.” 2013. Web. 17 Apr 2021.
Vancouver:
Wourms MJ. The Aryl Hydrocarbon Receptor Regulates an Essential
Transcriptional Element in the Immunoglobulin Heavy Chain
Gene. [Internet] [Masters thesis]. Wright State University; 2013. [cited 2021 Apr 17].
Available from: http://rave.ohiolink.edu/etdc/view?acc_num=wright1389551618.
Council of Science Editors:
Wourms MJ. The Aryl Hydrocarbon Receptor Regulates an Essential
Transcriptional Element in the Immunoglobulin Heavy Chain
Gene. [Masters Thesis]. Wright State University; 2013. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=wright1389551618
University of Helsinki
28.
Wikman, Harriet.
Individuella variationer i cancerkänslighet: genotypning av CYP1A1- och CYP2D6-generna hos lungcancerpatienter.
Degree: 1996, University of Helsinki
URL: http://hdl.handle.net/10138/157165
Subjects/Keywords: CYP1A1; CYP2D6; genpolymorfismer; tobaksrök; lungcancer; individuell cancerkänslighet; genotypning; Genetik; CYP1A1; CYP2D6; genpolymorfismer; tobaksrök; lungcancer; individuell cancerkänslighet; genotypning
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MLA ·
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CSE |
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to Zotero / EndNote / Reference
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APA (6th Edition):
Wikman, H. (1996). Individuella variationer i cancerkänslighet: genotypning av CYP1A1- och CYP2D6-generna hos lungcancerpatienter. (Thesis). University of Helsinki. Retrieved from http://hdl.handle.net/10138/157165
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Wikman, Harriet. “Individuella variationer i cancerkänslighet: genotypning av CYP1A1- och CYP2D6-generna hos lungcancerpatienter.” 1996. Thesis, University of Helsinki. Accessed April 17, 2021.
http://hdl.handle.net/10138/157165.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Wikman, Harriet. “Individuella variationer i cancerkänslighet: genotypning av CYP1A1- och CYP2D6-generna hos lungcancerpatienter.” 1996. Web. 17 Apr 2021.
Vancouver:
Wikman H. Individuella variationer i cancerkänslighet: genotypning av CYP1A1- och CYP2D6-generna hos lungcancerpatienter. [Internet] [Thesis]. University of Helsinki; 1996. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/10138/157165.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Wikman H. Individuella variationer i cancerkänslighet: genotypning av CYP1A1- och CYP2D6-generna hos lungcancerpatienter. [Thesis]. University of Helsinki; 1996. Available from: http://hdl.handle.net/10138/157165
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Helsinki
29.
Saarikoski, Sirkku.
Vierasainemetabolian merkitys keuhkosyövässä; in situ -hybridisaation soveltaminen CYP1A1-mRNA:n tunnistamiseen.
Degree: 1992, University of Helsinki
URL: http://hdl.handle.net/10138/158225
Subjects/Keywords: CYP1A1; P450IA1; in situ -hybridisaatio; keuhkokudos; mRNA; Perinnöllisyystiede; CYP1A1; P450IA1; in situ -hybridisaatio; keuhkokudos; mRNA
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APA ·
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MLA ·
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CSE |
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Manager
APA (6th Edition):
Saarikoski, S. (1992). Vierasainemetabolian merkitys keuhkosyövässä; in situ -hybridisaation soveltaminen CYP1A1-mRNA:n tunnistamiseen. (Thesis). University of Helsinki. Retrieved from http://hdl.handle.net/10138/158225
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Saarikoski, Sirkku. “Vierasainemetabolian merkitys keuhkosyövässä; in situ -hybridisaation soveltaminen CYP1A1-mRNA:n tunnistamiseen.” 1992. Thesis, University of Helsinki. Accessed April 17, 2021.
http://hdl.handle.net/10138/158225.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Saarikoski, Sirkku. “Vierasainemetabolian merkitys keuhkosyövässä; in situ -hybridisaation soveltaminen CYP1A1-mRNA:n tunnistamiseen.” 1992. Web. 17 Apr 2021.
Vancouver:
Saarikoski S. Vierasainemetabolian merkitys keuhkosyövässä; in situ -hybridisaation soveltaminen CYP1A1-mRNA:n tunnistamiseen. [Internet] [Thesis]. University of Helsinki; 1992. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/10138/158225.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Saarikoski S. Vierasainemetabolian merkitys keuhkosyövässä; in situ -hybridisaation soveltaminen CYP1A1-mRNA:n tunnistamiseen. [Thesis]. University of Helsinki; 1992. Available from: http://hdl.handle.net/10138/158225
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
30.
Fenile, Rogério [UNIFESP].
Avaliação da presença do polimorfismo Msp1 da CYP1A1 do citocromo P-450 em mulheres assintomáticas portadoras de cisto mamário.
Degree: 2010, Universidade Federal de São Paulo (UNIFESP)
URL: http://repositorio.unifesp.br/handle/11600/9033
► Made available in DSpace on 2015-07-22T20:49:31Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-12-02. Added 1 bitstream(s) on 2015-08-11T03:26:14Z : No. of bitstreams: 1…
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▼ Made available in DSpace on 2015-07-22T20:49:31Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-12-02. Added 1 bitstream(s) on 2015-08-11T03:26:14Z : No. of bitstreams: 1 Publico-12911.pdf: 1451194 bytes, checksum: 30932a96c61700c65652119d47fad0a7 (MD5)
Objetivo: o objetivo do estudo foi verificar a prevalência da alteração fibrocística da mama, na sua forma cística, dentre as diversas faixas etárias da população feminina e correlacionar a doença cística com a presença do polimorfismo Msp1 da CYP1A1 do citocromo P450 . Casuística e métodos: Estudo retrospectivo, caso-controle, desenvolvido entre março de 2005 a março de 2007. Submeteram-se a exame ultra-sonográfico, 204 mulheres, sendo divididas em dois grupos: 44 com doença cística mamária (casos) e 149 sem doenças mamárias (controles); 11 mulheres foram excluídas. Foi realizado estudo genético para a detecção do CYP1A1 através de reação em cadeia da polimerase e utilizado o teste de
Fisher e c2 para a análise estatística. Resultados: A doença cística mamária diagnosticada pelo ultra-som esteve presente em 22% da população estudada. Os cistos eram do tipo simples em 93%, múltiplos em 75% dos casos, e mediam 4-10 mm em 46%. A mama esquerda no quadrante súpero-lateral foi a localização mais freqüente. O perfil epidemiológico-clínico dessas mulheres foi: branca, faixa etária de 41-50 anos, ciclos menstruais regulares, multípara e com queixa de mastalgia. Na análise genética do CYP1A1, observamos homozigoto selvagem numa freqüência de 68,2% no grupo casos e 66% no controle; heterozigotos 31,28% no grupo estudo e 26,8% no controle.Não houve aparecimento do homozigoto mutado no grupo casos surgindo como 7,2% no controle. Não houve diferença estatisticamente significante entre os grupos (p = 0,42). Conclusão: A prevalência e quase todo o perfil epidemiológico da doença cística mamária foram compatíveis com a literatura. Houve maior freqüência de heterozigotos mutados no
grupo de casos, porém não de homozigotos.Não houve associação estatisticamente significante entre o polimorfismo da CYP1A1 e a doença fibrocística mamária na sua forma cística.
TEDE
Advisors/Committee Members: Universidade Federal de São Paulo (UNIFESP), Nazário, Afonso Celso Pinto [UNIFESP].
Subjects/Keywords: CYP1A1; Cisto mamário; Polimorfismo; Doença da mama fibrocística; Breast cyst; CYP1A1; Polymorphism; Fibrocystic breast disease
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APA (6th Edition):
Fenile, R. [. (2010). Avaliação da presença do polimorfismo Msp1 da CYP1A1 do citocromo P-450 em mulheres assintomáticas portadoras de cisto mamário. (Masters Thesis). Universidade Federal de São Paulo (UNIFESP). Retrieved from http://repositorio.unifesp.br/handle/11600/9033
Chicago Manual of Style (16th Edition):
Fenile, Rogério [UNIFESP]. “Avaliação da presença do polimorfismo Msp1 da CYP1A1 do citocromo P-450 em mulheres assintomáticas portadoras de cisto mamário.” 2010. Masters Thesis, Universidade Federal de São Paulo (UNIFESP). Accessed April 17, 2021.
http://repositorio.unifesp.br/handle/11600/9033.
MLA Handbook (7th Edition):
Fenile, Rogério [UNIFESP]. “Avaliação da presença do polimorfismo Msp1 da CYP1A1 do citocromo P-450 em mulheres assintomáticas portadoras de cisto mamário.” 2010. Web. 17 Apr 2021.
Vancouver:
Fenile R[. Avaliação da presença do polimorfismo Msp1 da CYP1A1 do citocromo P-450 em mulheres assintomáticas portadoras de cisto mamário. [Internet] [Masters thesis]. Universidade Federal de São Paulo (UNIFESP); 2010. [cited 2021 Apr 17].
Available from: http://repositorio.unifesp.br/handle/11600/9033.
Council of Science Editors:
Fenile R[. Avaliação da presença do polimorfismo Msp1 da CYP1A1 do citocromo P-450 em mulheres assintomáticas portadoras de cisto mamário. [Masters Thesis]. Universidade Federal de São Paulo (UNIFESP); 2010. Available from: http://repositorio.unifesp.br/handle/11600/9033
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Open Access Theses and Dissertations