+publisher:"Texas A&M University" +contributor:("Donnelly, Kirby C.")

1. Naufal, Ziad Sami. Biomarkers of exposure to complex environmental mixtures.

Degree: PhD, Toxicology, 2009, Texas A&M University

URL: http://hdl.handle.net/1969.1/ETD-TAMU-3284

► Maternal exposure to genotoxic chemicals may produce a variety of adverse birth outcomes. Depending on the dose and duration of exposure, adverse birth outcomes can… (more)

▼ Maternal exposure to genotoxic chemicals may produce a variety of adverse birth outcomes. Depending on the dose and duration of exposure, adverse birth outcomes can range from premature or low-birth weight, to congenital abnormalities including neural tube defects (NTDs). The research described in this dissertation focused on several rural counties in Shanxi province, China. Shanxi has one of the highest rates of NTDs in the world. In 2005, the incidence of NTDs in the study counties ranged from 8 to 24 cases per 1,000 births. While some of these birth defects are likely to be related to nutrition, it is also suggested that environmental factors play a significant role. One such factor includes polycyclic aromatic hydrocarbon (PAH) exposure as a result of combustion of coal for indoor heating and cooking. Human populations in Shanxi depend heavily on coal as their main source of energy. This study determined the concentrations of PAHs in house dust, venous blood and placenta of study participants. Dust was collected from homes in the study site. Carcinogenic PAH levels in dust collected from kitchen floors ranged from 12 to 2,000 µg/m2. The genotoxic potential of dust was confirmed by shortterm bioassays. Median concentrations of total PAHs in placenta from children born with NTDs were elevated compared to matched controls and appeared to be associated with the risk of having a child with a NTD. Tobacco smoking was not associated with elevated levels of PAH biomarkers in this study population. Levels of bulky DNA adducts in placenta have also been quantified using 32P-postlabeling. Adduct levels do not appear to be significantly different between cases and controls and were not associated with deletions in enzymes GSTM1 or GSTT1. These data suggest that children born with NTDs may be at increased risk due to exposure to genotoxic PAHs. Studies with a larger number of subjects are needed to further elucidate the relationship between PAH exposure and adverse birth outcomes. Advisors/Committee Members: Donnelly, Kirby C. (advisor), McDonald, Thomas J. (advisor), Carozza, Susan E. (committee member), Safe, Stephen H. (committee member).

Subjects/Keywords: PAHs; Biomarkers

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APA (6^th Edition):

Naufal, Z. S. (2009). Biomarkers of exposure to complex environmental mixtures. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/ETD-TAMU-3284

Chicago Manual of Style (16^th Edition):

Naufal, Ziad Sami. “Biomarkers of exposure to complex environmental mixtures.” 2009. Doctoral Dissertation, Texas A&M University. Accessed January 22, 2021. http://hdl.handle.net/1969.1/ETD-TAMU-3284.

MLA Handbook (7^th Edition):

Naufal, Ziad Sami. “Biomarkers of exposure to complex environmental mixtures.” 2009. Web. 22 Jan 2021.

Vancouver:

Naufal ZS. Biomarkers of exposure to complex environmental mixtures. [Internet] [Doctoral dissertation]. Texas A&M University; 2009. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-3284.

Council of Science Editors:

Naufal ZS. Biomarkers of exposure to complex environmental mixtures. [Doctoral Dissertation]. Texas A&M University; 2009. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-3284

2. Naspinski, Christine S. Toxicity Analysis of Polycyclic Aromatic Hydrocarbon Mixtures.

Degree: PhD, Toxicology, 2010, Texas A&M University

URL: http://hdl.handle.net/1969.1/ETD-TAMU-2009-05-310

► Polycyclic aromatic hydrocarbons (PAHs) are widely distributed in the environment and are generated by many sources. Though the potential of PAH-rich mixtures to cause health… (more)

▼ Polycyclic aromatic hydrocarbons (PAHs) are widely distributed in the environment and are generated by many sources. Though the potential of PAH-rich mixtures to cause health effects has been known for almost a century, there are still unanswered questions about the levels of PAHs in the environment, the potential for human exposure to PAHs, the health effects associated with exposure, and how genetic susceptibility influences the extent of health effects in individuals. The first objective of this research was to quantify concentrations of PAHs in samples of settled house dust collected from homes in Azerbaijan, China, and Texas. The trends of PAH surface loadings and percentage of carcinogenic PAHs were China > Azerbaijan > Texas, indicating that the risk of health effects from exposure to PAHs in house dust is highest in the Chinese population and lowest in the Texas population. PAHs in China and Azerbaijan were derived mainly from combustion sources; Texas PAHs were derived from unburned fossil fuels such as petroleum. The second objective of this research was to investigate the effect of pregnane X receptor (PXR) on the genotoxicity of benzo[a]pyrene (BaP). BaP treatment resulted in significantly lower DNA adduct levels in PXR-transfected HepG2 cells than in parental HepG2 cells. Total GST enzymatic activity and mRNA levels of several metabolizing enyzmes were significantly higher in cells overexpressing PXR. These results suggest that PXR protects cells against DNA damage by PAHs such as BaP, possibly through a coordinated regulation of genes involved in xenobiotic metabolism. The third objective of this research was to investigate biomarkers of exposure in house mice (Mus musculus) exposed to PAH mixtures in situ. Mice and soil were collected near homes in Sumgayit and Khizi, Azerbaijan. Mean liver adduct levels were significantly higher in Khizi than in Sumgayit. Mean lung and kidney adduct levels were similar in the two regions. The DNA lesions detected may be a combination of environmentally-induced DNA adducts and naturally-occurring I-compounds. PAHs were present at background levels in soils from both Khizi and Sumgayit. It appears that health risks posed to rodents by soil-borne PAHs are low in these two areas. Advisors/Committee Members: Donnelly, Kirby C. (advisor), McDonald, Thomas J. (advisor), Autenrieth, Robin L. (committee member), Tian, Yanan (committee member).

Subjects/Keywords: PAH; PXR; Mus musculus; house dust; benzo[a]pyrene

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APA (6^th Edition):

Naspinski, C. S. (2010). Toxicity Analysis of Polycyclic Aromatic Hydrocarbon Mixtures. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/ETD-TAMU-2009-05-310

Chicago Manual of Style (16^th Edition):

Naspinski, Christine S. “Toxicity Analysis of Polycyclic Aromatic Hydrocarbon Mixtures.” 2010. Doctoral Dissertation, Texas A&M University. Accessed January 22, 2021. http://hdl.handle.net/1969.1/ETD-TAMU-2009-05-310.

MLA Handbook (7^th Edition):

Naspinski, Christine S. “Toxicity Analysis of Polycyclic Aromatic Hydrocarbon Mixtures.” 2010. Web. 22 Jan 2021.

Vancouver:

Naspinski CS. Toxicity Analysis of Polycyclic Aromatic Hydrocarbon Mixtures. [Internet] [Doctoral dissertation]. Texas A&M University; 2010. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2009-05-310.

Council of Science Editors:

Naspinski CS. Toxicity Analysis of Polycyclic Aromatic Hydrocarbon Mixtures. [Doctoral Dissertation]. Texas A&M University; 2010. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2009-05-310

3. Abdel Rahim, Ma'en Ahmad. Gene silencing in cancer cells using siRNA : genetic and functional studies.

Degree: PhD, Toxicology, 2004, Texas A&M University

URL: http://hdl.handle.net/1969.1/218

► Sequence-specific small interfering RNA (siRNA) duplexes can be used for gene silencing in mammalian cells and as mechanistic probes for determining gene function. Transfection of… (more)

▼ Sequence-specific small interfering RNA (siRNA) duplexes can be used for gene silencing in mammalian cells and as mechanistic probes for determining gene function. Transfection of siRNA for specificity protein 1 (Sp1) in MCF-7 or ZR-75 cells decreased Sp1 protein in nuclear extracts, and immunohistochemical analysis showed that Sp1 protein in transfected MCF-7 cells was barely detectable. Decreased Sp1 protein in MCF-7 was accompanied by a decrease in basal and estrogen-induced transactivation and cell cycle progression. These results clearly demonstrate the key role of Sp1 protein in regulating growth and gene expression of breast cancer cells. The aryl hydrocarbon (AhR) is a ligand-activated nuclear transcription factor. siRNA for the AhR decreased TCDD-induced CYP1A1 protein, CYP1A1dependent activity, and luciferase activity in cells transfected with an Ah-responsive construct. 17β-Estradiol (E2) induces proliferation of MCF-7 cells, and this response is inhibited in cells cotreated with E2 plus TCDD. The effects of TCDD on E2-induced cell cycle progression were partially blocked in MCF-7 cells transfected with siRNA for AhR. The decrease in AhR protein in MCF-7 cells was also accompanied by increased G0/G1 → S phase progression. Surprisingly, TCDD alone induced G0/G1 → S phase progression and exhibited estrogenic activity in MCF-7 cells transfected with siRNA for the AhR. In contrast, degradation of the AhR in HepG2 liver cancer cells resulted in decreased G0/G1 → S phase progression, and this was accompanied by decreased expression of cyclin D1, cyclin E, cdk2 and cdk4. In the absence of ligand, the AhR exhibits growth inhibitory (MCF-7) and growth promoting (HepG2) activity that is cell context-dependent. Sp family proteins play a complex role in regulation of pancreatic cancer cells growth and expression of genes required for growth, angiogenesis and apoptosis. Sp1, Sp3 and Sp4 cooperatively activate VEGF promoter constructs in these cells; however, only Sp3 regulates cell proliferation. siRNA for Sp3 inhibits phosphorylation of retinoblastoma protein, blocks G0/G1 → S phase progression of Panc-1 cells, and upregulates p27 protein/promoter activity. Thus, Sp3 plays a critical role in angiogenesis (VEGF upregulation) and the proliferation of Panc-1 cells by a novel mechanism of Sp3-dependent suppression of the cyclin-dependent kinase inhibitor p27. Advisors/Committee Members: Safe, Stephen H. (advisor), Phillips, Timothy D. (committee member), Porter, Weston W. (committee member), Donnelly, Kirby C. (committee member).

Subjects/Keywords: RNAi; siRNA; Sp proteins; TCDD; AhR; ARNT; VEGF; breast cancer; pancreatic cancer.

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APA (6^th Edition):

Abdel Rahim, M. A. (2004). Gene silencing in cancer cells using siRNA : genetic and functional studies. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/218

Chicago Manual of Style (16^th Edition):

Abdel Rahim, Ma'en Ahmad. “Gene silencing in cancer cells using siRNA : genetic and functional studies.” 2004. Doctoral Dissertation, Texas A&M University. Accessed January 22, 2021. http://hdl.handle.net/1969.1/218.

MLA Handbook (7^th Edition):

Abdel Rahim, Ma'en Ahmad. “Gene silencing in cancer cells using siRNA : genetic and functional studies.” 2004. Web. 22 Jan 2021.

Vancouver:

Abdel Rahim MA. Gene silencing in cancer cells using siRNA : genetic and functional studies. [Internet] [Doctoral dissertation]. Texas A&M University; 2004. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1969.1/218.

Council of Science Editors:

Abdel Rahim MA. Gene silencing in cancer cells using siRNA : genetic and functional studies. [Doctoral Dissertation]. Texas A&M University; 2004. Available from: http://hdl.handle.net/1969.1/218

Texas A&M University

4. Desai, Anuradha M. Biodegradability of select polycyclic aromatic hydrocarbon (pah) mixtures.

Degree: MS, Civil Engineering, 2007, Texas A&M University

URL: http://hdl.handle.net/1969.1/4697

► Polycyclic aromatic hydrocarbons (PAHs) are environmentally significant because of their ubiquity and the toxicity of some. Their recalcitrance and persistence makes them problematic environmental contaminants.… (more)

▼ Polycyclic aromatic hydrocarbons (PAHs) are environmentally significant because of their ubiquity and the toxicity of some. Their recalcitrance and persistence makes them problematic environmental contaminants. Microbial degradation is considered to be the primary mechanism of PAH removal from the environment. Biodegradation kinetics of individual PAHs by pure and mixed cultures have been reported by several researchers. However, contaminated sites commonly have complex mixtures of PAHs whose individual biodegradability may be altered in mixtures. Biodegradation kinetics for fluorene, naphthalene, 1,5-dimethylnaphthalene and 1- methylfluorene were evaluated in sole substrate systems, binary and ternary systems using Sphingomonas paucimobilis EPA505. The Monod model was fitted to the data from the sole substrate experiments to yield biokinetic parameters, (qmax and Ks). The first order rate constants (qmax/Ks) for fluorene, naphthalene and 1,5- dimethylnaphthalene were comparable, although statistically different. However, affinity constants for the three compounds were not comparable. Binary and ternary experiments indicated that the presence of another PAH retards the biodegradation of the co-occurring PAH. Antagonistic interactions between substrates were evident in the form of competitive inhibition, demonstrated mathematically by the Monod multisubstrate model. This model appropriately predicted the biodegradation kinetics in mixtures using the sole substrate parameters, validating the hypothesis of common enzyme systems. Competitive inhibition became pronounced under conditions of: Ks1 << Ks, S1 >> Ks1 and S1 >> S. Experiments with equitable concentrations of substrates demonstrated the effect of concentration on competitive inhibition. Ternary experiments with naphthalene, 1,5-dimethylnapthalene and 1-methylfluorene revealed preferential degradation, where depletion of naphthalene and 1,5-dimethylnapthalene proceeded only after the complete removal of 1-methylfluorene. The substrate interactions observed in binary and ternary mixtures require a multisubstrate model to account for simultaneous degradation of substrates. However, developing models that account for sequential degradation may be useful in scenarios where PAHs may not be competitive substrates. These mixture results prove that substrate interactions must be considered in designing effective bioremediation strategies and that sole substrate performance is limited in predicting biodegradation kinetics of complex mixtures. Advisors/Committee Members: Autenrieth, Robin L (advisor), Donnelly, Kirby C (committee member), Kramer, Timothy A (committee member).

Subjects/Keywords: Biodegradability; PAH mixtures

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Desai, A. M. (2007). Biodegradability of select polycyclic aromatic hydrocarbon (pah) mixtures. (Masters Thesis). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/4697

Chicago Manual of Style (16^th Edition):

Desai, Anuradha M. “Biodegradability of select polycyclic aromatic hydrocarbon (pah) mixtures.” 2007. Masters Thesis, Texas A&M University. Accessed January 22, 2021. http://hdl.handle.net/1969.1/4697.

MLA Handbook (7^th Edition):

Desai, Anuradha M. “Biodegradability of select polycyclic aromatic hydrocarbon (pah) mixtures.” 2007. Web. 22 Jan 2021.

Vancouver:

Desai AM. Biodegradability of select polycyclic aromatic hydrocarbon (pah) mixtures. [Internet] [Masters thesis]. Texas A&M University; 2007. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1969.1/4697.

Council of Science Editors:

Desai AM. Biodegradability of select polycyclic aromatic hydrocarbon (pah) mixtures. [Masters Thesis]. Texas A&M University; 2007. Available from: http://hdl.handle.net/1969.1/4697

Texas A&M University

5. Kern, Rory James. Enzyme-based detoxification of organophosphorus neurotoxic pesticides and chemical warfare agents.

Degree: PhD, Toxicology, 2009, Texas A&M University

URL: http://hdl.handle.net/1969.1/ETD-TAMU-2118

► There are some 15,000 known organophosphorus chemicals. Some of these OP’s, including VX and paraoxon, demonstrate an acute neurotoxicity due to the inhibition of cholinergic… (more)

▼ There are some 15,000 known organophosphorus chemicals. Some of these OP’s, including VX and paraoxon, demonstrate an acute neurotoxicity due to the inhibition of cholinergic enzymes. Organophosphorus chemical warfare agents and pesticide neurotoxins are subject to hydrolysis by OP degrading enzymes. To be useful as a bioremediation or anti-chemical warfare agent, the enzyme must be tailored for, and integrated into, a practical application platform. Several studies have established enzyme-based countermeasures, describing such diverse applications as decontaminating foams for surface remediation, encapsulating enzyme with liposome for in vivo therapy, enzyme attachments to surfaces for biosensors and development of a corn expression system for large-scale enzyme production. The goal of the research described here is to select, investigate and improve the operational potential of organophosphate-degrading enzymes including Organophosphorus Hydrolase (OPH, 3.1.8.1) and Organophosphorus Acid Anhydrolase (OPAA, 3.1.8.2). Using saturation kinetics, the catalytic efficiencies of these two major detoxification enzymes were characterized with substrates representing each class of OP neurotoxin, phosphotriester, phosphothioate and phosphofluoridate. OPH presents superior kinetic parameters with each OP class tested. Variants of OPH were created to increase the operational effectiveness of OP hydrolytic enzymes against phosphorothioates. An H254S/H257L mutation in the active site resulted in an improvement in the kinetics (kcat/KM) for the phosphorothioate, demeton-S. To screen potential vascular protection therapies, an in vitro protocol was developed to predict enzymatic effectiveness for protection of acetylcholinesterase from acute OP-inhibition. The protection abilities of the enzymes were directly related to their second order rate constants as inhibitory levels of OP are below the KM of the enzymes. Consideration of contaminant nature concentration and enzyme kinetic parameters, kcat and KM, is critical to understanding decontamination and effective use of enzyme technology. These technologies continue to develop and provide promising new decontamination tools for OP compounds. Advisors/Committee Members: Wild, James R. (advisor), Donnelly, Kirby C. (committee member), Phillips, Timothy D. (committee member), Wales, Melinda E. (committee member).

Subjects/Keywords: Enzyme; Organophosphorus; Chemical Warfare Agents; Remediation; Treatment

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kern, R. J. (2009). Enzyme-based detoxification of organophosphorus neurotoxic pesticides and chemical warfare agents. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/ETD-TAMU-2118

Chicago Manual of Style (16^th Edition):

Kern, Rory James. “Enzyme-based detoxification of organophosphorus neurotoxic pesticides and chemical warfare agents.” 2009. Doctoral Dissertation, Texas A&M University. Accessed January 22, 2021. http://hdl.handle.net/1969.1/ETD-TAMU-2118.

MLA Handbook (7^th Edition):

Kern, Rory James. “Enzyme-based detoxification of organophosphorus neurotoxic pesticides and chemical warfare agents.” 2009. Web. 22 Jan 2021.

Vancouver:

Kern RJ. Enzyme-based detoxification of organophosphorus neurotoxic pesticides and chemical warfare agents. [Internet] [Doctoral dissertation]. Texas A&M University; 2009. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2118.

Council of Science Editors:

Kern RJ. Enzyme-based detoxification of organophosphorus neurotoxic pesticides and chemical warfare agents. [Doctoral Dissertation]. Texas A&M University; 2009. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2118

Texas A&M University

6. Zhang, Shu. Role of estrogen receptor alpha (ER alpha) insulin-like growth factor (IGF)-I-induced responses in MCF-7 breast cancer cells.

Degree: PhD, Toxicology, 2009, Texas A&M University

URL: http://hdl.handle.net/1969.1/ETD-TAMU-2603

► Insulin-like growth factor-I (IGF-I) is a mitogenic polypeptide that induces proliferation and activation of kinase pathways in MCF-7 breast cancer cells. The role of estrogen… (more)

▼ Insulin-like growth factor-I (IGF-I) is a mitogenic polypeptide that induces proliferation and activation of kinase pathways in MCF-7 breast cancer cells. The role of estrogen receptor α (ERα) in mediating responses induced by IGF-I was investigated in cells transfected with small inhibitory RNA for ERα (iERα) or cotreated with the pure antiestrogen ICI 182780. The results showed that IGF-I-dependent phosphorylation of Akt and MAPK, induction of G1–S-phase progression and enhanced expression of cyclin D1 and cyclin E were dependent on ERα. Moreover, these IGF-I-induced responses were also inhibited by the antiestrogen ICI 182780, suggesting that the effects of ICI 182780 as an inhibitor of IGF-I induced responses in breast cancer cells are primarily related to downregulation of ERα. Chemoprotective phytochemicals exhibit multiple activities and interact with several cellular receptors, including the aryl hydrocarbon receptor (AhR). We investigated the AhR agonist/antagonist activities of the following flavonoids: chrysin, phloretin, kaempferol, galangin, naringenin, genistein, quercetin, myricetin, luteolin, baicalein, daidzein, apigenin, and diosmin, in MCF-7 breast cancer cells, HepG2 human liver cells and mouse Hepa-1 cells. The dietary phytochemicals exhibited substantial cell context–dependent AhR agonist as well as antagonist activities, and these are factors that must be considered in risk assessment of overall exposures to AhR agonists. Halogenated aromatic hydrocarbons (HAHs) such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 1,2,3,7,8- pentachlorodibenzo-p-dioxin (PeCDD), 3,3’,4,4’,5-pentachlorobiphenyl (PCBP), 2,3,7,8- tetrachlorodibenzofuran (TCDF) and 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) bind and activate the aryl hydrocarbon receptor (AhR). It has been assumed that these compounds only differ in their potencies. The SAhRM-like activity of the 5 HAHs was investigated by determining ligand structure dependent differences in their induction of CYP1A1 and interactions of the AhR with a series of coactivators in a mammalian two-hybrid assay in three AhR-responsive cell lines, including mouse Hepa-1, Human HEK293 and human Panc1 cells. There were multiple structure-dependent differences in activation of luciferase activity in these cell lines transfected with VP-AhR and six different GAL4-coactivator chimeras and a GAL4-response element-luciferase promoter construct. The results show that HAHs selectively interact with coactivators and these interactions are dependent on cell-context, and even among HAHs, these compounds exhibit selective receptor modulator activity. Advisors/Committee Members: Safe, Stephen H. (advisor), Burghardt, Robert C. (committee member), Donnelly, Kirby C. (committee member), Phillips, Timothy D. (committee member).

Subjects/Keywords: IGF-I; breast cancer

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zhang, S. (2009). Role of estrogen receptor alpha (ER alpha) insulin-like growth factor (IGF)-I-induced responses in MCF-7 breast cancer cells. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/ETD-TAMU-2603

Chicago Manual of Style (16^th Edition):

Zhang, Shu. “Role of estrogen receptor alpha (ER alpha) insulin-like growth factor (IGF)-I-induced responses in MCF-7 breast cancer cells.” 2009. Doctoral Dissertation, Texas A&M University. Accessed January 22, 2021. http://hdl.handle.net/1969.1/ETD-TAMU-2603.

MLA Handbook (7^th Edition):

Zhang, Shu. “Role of estrogen receptor alpha (ER alpha) insulin-like growth factor (IGF)-I-induced responses in MCF-7 breast cancer cells.” 2009. Web. 22 Jan 2021.

Vancouver:

Zhang S. Role of estrogen receptor alpha (ER alpha) insulin-like growth factor (IGF)-I-induced responses in MCF-7 breast cancer cells. [Internet] [Doctoral dissertation]. Texas A&M University; 2009. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2603.

Council of Science Editors:

Zhang S. Role of estrogen receptor alpha (ER alpha) insulin-like growth factor (IGF)-I-induced responses in MCF-7 breast cancer cells. [Doctoral Dissertation]. Texas A&M University; 2009. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2603

Texas A&M University

7. Phillips, Tracie Denise. Genotoxicity of complex chemical mixtures.

Degree: PhD, Toxicology, 2009, Texas A&M University

URL: http://hdl.handle.net/1969.1/ETD-TAMU-1208

► Complex chemical mixtures are ubiquitous in the environment. Humans are frequently exposed to these mixtures; therefore, it is important to understand potential interactions of chemical… (more)

▼ Complex chemical mixtures are ubiquitous in the environment. Humans are frequently exposed to these mixtures; therefore, it is important to understand potential interactions of chemical mixtures. Mixture interactions may influence the absorption, distribution, metabolism or excretion of the components of a complex mixture. The research conducted for this dissertation has coupled chemical fractionation with in vitro and in vivo bioassays to assess the potential carcinogenic risk of complex mixtures. A non-aqueous phase liquid from a wood treatment plant was separated into acid (AF), base (BF) and neutral fractions (NF). The NF was further enriched using column chromatography to produce a polychlorinated dinbenzo-p-dioxin (PCDD) and a polycyclic aromatic hydrocarbon (PAH) fraction. The genotoxicity of these mixtures were assessed via analytical quantification, in vitro (Salmonella microsome and E. coli prophage induction) and in vivo (32P-postlabeling) bioassays. The NF was further tested to measure bulky DNA adducts and induction of tumor formation. The AF contained the highest level of pentachlorophenol and the highest concentration of total PAHs. Although the carcinogenic PAHs were highest in the PCDD fraction, the highest concentrations of benzo(a)pyrene (BAP), indeno(1,2,3-cd)pyrene and dibenz(a,h)anthracene were detected in the PAH fraction. A positive genotoxic response in Salmonella was induced by the crude extract, the PAH and BF, whereas the AF and BF induced a positive response in the E. coli assay. In vivo, the PAH fraction induced the highest DNA adduct frequencies in the lung. The NF, reconstituted mixture (RM) (which includes equivalent concentrations of seven carcinogenic PAHs in the NF), BAP and the NF amended with BAP (NF+BAP) were all tested in an infant mouse model. At the highest dose, after a 24 hr exposure, NF+BAP had the highest total DNA adducts measured in liver which was three to seven times higher than with other treatments. Adduct levels were comparable to the control after 280 days. The highest incidence of tumors was observed in the liver. At the high dose, NF+BAP elicited the highest incidence of tumors. The results of this research confirm previous studies and indicate that the carcinogenic potential of PAH mixtures may be greater than predicted by chemical analysis. Advisors/Committee Members: Donnelly, Kirby C. (advisor), Autenrieth, Robin L. (committee member), McDonald, Thomas J. (committee member), Safe, Stephen S. (committee member).

Subjects/Keywords: PAHs; Genotoxicity

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APA (6^th Edition):

Phillips, T. D. (2009). Genotoxicity of complex chemical mixtures. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/ETD-TAMU-1208

Chicago Manual of Style (16^th Edition):

Phillips, Tracie Denise. “Genotoxicity of complex chemical mixtures.” 2009. Doctoral Dissertation, Texas A&M University. Accessed January 22, 2021. http://hdl.handle.net/1969.1/ETD-TAMU-1208.

MLA Handbook (7^th Edition):

Phillips, Tracie Denise. “Genotoxicity of complex chemical mixtures.” 2009. Web. 22 Jan 2021.

Vancouver:

Phillips TD. Genotoxicity of complex chemical mixtures. [Internet] [Doctoral dissertation]. Texas A&M University; 2009. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-1208.

Council of Science Editors:

Phillips TD. Genotoxicity of complex chemical mixtures. [Doctoral Dissertation]. Texas A&M University; 2009. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-1208

Texas A&M University

8. Hill, Denise Suzanne. Investigations into arsenate-induced neural tube defects in a mouse model.

Degree: PhD, Toxicology, 2009, Texas A&M University

URL: http://hdl.handle.net/1969.1/ETD-TAMU-3274

► Neural tube defects (NTDs) are malformations affecting about 2.6/1000 births worldwide, and 1/1000 in the United States. Their etiology remains unknown, and is likely due… (more)

▼ Neural tube defects (NTDs) are malformations affecting about 2.6/1000 births worldwide, and 1/1000 in the United States. Their etiology remains unknown, and is likely due to interaction of genetic susceptibility factors with environmental exposure. Of the many environmental agents considered to potentially contribute to NTD risk, arsenic is one that is surrounded in controversy. We have developed a model system utilizing maternal intraperitoneal (I.P.) exposure on E7.5 and E8.5 to As 9.6 mg/kg (as sodium arsenate) in a normal inbred mouse strain, LM/Bc/Fnn, that is sensitive to arsenate-induced exencephaly. We investigated arsenate induced gene expression changes using DNA microarrays of embryonic anterior neural tube tissue, as well as monitoring of metabolic function in conjunction with the administration of select compounds to rescue the normal phenotype. Finally, to address questions concerning the importance of route of administration and potential maternal toxicity, a teratology study was performed using three arsenate doses administered orally. Regarding the gene expression study, we identified several candidate genes and ontology groups that may be responsible for arsenate’s teratogenicity. Genes include: engrailed 1 (En-1), platelet derived growth factor receptor alpha (Pdgfrα) and ephrinA7 (EphA7). Gene ontology groups identified include oxidative phosphorylation, redox response, and regulation of I-kappaB kinase/NF-kappaB cascade. Acute arsenate exposure induced disruption of mitochondrial function and dependent glucose homeostasis: subsequent hyperglycemia was teratogenic. Maternal treatment with insulin or n-acetyl cysteine, an antioxidant and precursor of glutathione synthesis, proved highly successful in rescuing both the normal phenotype, and to differing degree, the maternal hyperglycemia. Maternal oral arsenate administration also resulted in exencephaly, with exposed embryos exhibiting a positive linear trend with arsenate dosage. There were also linear trends in the relationships between arsenate dose and anomalies involving several components of the axial skeleton: the vertebrae and calvarium. There was no evidence of maternal toxicity as shown by lack of differences in maternal body weight gain, liver, and kidney weights. In conclusion, maternal arsenate exposure (regardless of exposure route) was teratogenic in our model, primarily causing NTDs. Responsible mechanisms may involve disruption of redox and glucose homeostasis as well as expression of established NTD candidate genes. Advisors/Committee Members: Donnelly, Kirby C. (advisor), Finnell, Richard H. (advisor), Mitchell, Laura E. (committee member), Safe, Stephen H. (committee member).

Subjects/Keywords: arsenic; teratogen; arsenate; NTD; environmental; neural tube defect

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APA (6^th Edition):

Hill, D. S. (2009). Investigations into arsenate-induced neural tube defects in a mouse model. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/ETD-TAMU-3274

Chicago Manual of Style (16^th Edition):

Hill, Denise Suzanne. “Investigations into arsenate-induced neural tube defects in a mouse model.” 2009. Doctoral Dissertation, Texas A&M University. Accessed January 22, 2021. http://hdl.handle.net/1969.1/ETD-TAMU-3274.

MLA Handbook (7^th Edition):

Hill, Denise Suzanne. “Investigations into arsenate-induced neural tube defects in a mouse model.” 2009. Web. 22 Jan 2021.

Vancouver:

Hill DS. Investigations into arsenate-induced neural tube defects in a mouse model. [Internet] [Doctoral dissertation]. Texas A&M University; 2009. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-3274.

Council of Science Editors:

Hill DS. Investigations into arsenate-induced neural tube defects in a mouse model. [Doctoral Dissertation]. Texas A&M University; 2009. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-3274

Texas A&M University

9. Armstrong, Charles David. Elucidating the chemical and thermal unfolding profiles of organophosphorus hydrolase and increasing its operational stability.

Degree: PhD, Biochemistry, 2009, Texas A&M University

URL: http://hdl.handle.net/1969.1/ETD-TAMU-1237

► Organophosphorus hydrolase (OPH, EC 3.1.8.1) is a homodimeric enzyme that has been observed to unfold via a three-state unfolding pathway (N2* ↔ I2 ↔ 2U)… (more)

▼ Organophosphorus hydrolase (OPH, EC 3.1.8.1) is a homodimeric enzyme that has been observed to unfold via a three-state unfolding pathway (N2* ↔ I2 ↔ 2U) under chemical denaturing conditions. The dimeric intermediate (I2) is catalytically inactive and, although this enzyme has a very large overall conformational stability (~40 kcal/mol), it takes only a small amount of energy (~4 kcal/mol) to unfold this enzyme into its inactive form. So that this enzyme might be engineered as a more effective tool for nerve agent countermeasures and bioremediation purposes, its operational stability (the energy required to unfold the enzyme from its active, dimeric state to its inactive, dimeric state) must be increased. For this purpose, it is necessary to understand how the enzyme unfolds into its inactive, intermediate state. As tryptophan residues are sensitive probes of the microenvironment surrounding the residue, enzyme variants consisting of one tryptophan per subunit were constructed. Unfortunately, these variant enzymes did not fold into active conformations, and so could not be used to develop an accurate unfolding profile for the wild type enzyme. Limited proteolysis of OPH by thermolysin revealed detailed information on the unfolding process of OPH in chemical and thermal denaturing conditions. Mild denaturing conditions induced an initial enhancement of activity with a subsequent loss of catalytic activity upon more aggressive treatment. Under thermal conditions from 35 – 55 °C, the enzyme developed a well populated and active intermediate that displayed maximal activity. Similarly, the enzyme displayed maximal activity when incubated at 1.0 M urea. The regions of the enzyme, which became accessible to proteolysis at 45 °C and 1 M urea, were identical. This suggested that increased flexibility of these regions was coupled with the increase in the enzyme’s catalytic activity. Two regions that were determined by limited proteolysis to be the first to unfold were bridged with a novel disulfide bond. The result was an enzyme with an increased operational stability and resistance to proteolysis. This enzyme retained approximately 70% of its original activity in 8 M urea while no activity remained for the wild type enzyme when incubated in 6.5 M urea. Advisors/Committee Members: Wild, James R. (advisor), Donnelly, Kirby C. (committee member), Raushel, Frank M. (committee member), Scholtz, J. Martin (committee member).

Subjects/Keywords: Organophosphorus Hydrolase; Unfolding Profile

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APA (6^th Edition):

Armstrong, C. D. (2009). Elucidating the chemical and thermal unfolding profiles of organophosphorus hydrolase and increasing its operational stability. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/ETD-TAMU-1237

Chicago Manual of Style (16^th Edition):

Armstrong, Charles David. “Elucidating the chemical and thermal unfolding profiles of organophosphorus hydrolase and increasing its operational stability.” 2009. Doctoral Dissertation, Texas A&M University. Accessed January 22, 2021. http://hdl.handle.net/1969.1/ETD-TAMU-1237.

MLA Handbook (7^th Edition):

Armstrong, Charles David. “Elucidating the chemical and thermal unfolding profiles of organophosphorus hydrolase and increasing its operational stability.” 2009. Web. 22 Jan 2021.

Vancouver:

Armstrong CD. Elucidating the chemical and thermal unfolding profiles of organophosphorus hydrolase and increasing its operational stability. [Internet] [Doctoral dissertation]. Texas A&M University; 2009. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-1237.

Council of Science Editors:

Armstrong CD. Elucidating the chemical and thermal unfolding profiles of organophosphorus hydrolase and increasing its operational stability. [Doctoral Dissertation]. Texas A&M University; 2009. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-1237

Texas A&M University

10. Gu, Xinsheng. Regulation of cytochrome P450 3A4 gene expression through modulating pregnane X receptor transcriptional activity by NF-ꢬ aryl hydrocarbon receptor and xenobiotics.

Degree: PhD, Toxicology, 2009, Texas A&M University

URL: http://hdl.handle.net/1969.1/ETD-TAMU-1630

► Cytochrome P450 3A4 (CYP3A4) is a key enzyme responsible for the metabolism of drugs and endogenous compounds in human liver and intestine. CYP3A4 gene expression… (more)

▼ Cytochrome P450 3A4 (CYP3A4) is a key enzyme responsible for the metabolism of drugs and endogenous compounds in human liver and intestine. CYP3A4 gene expression is mainly regulated by Pregnane X receptor (PXR) which is a ligand-dependent nuclear receptor. It is a long-standing observation that inflammatory responses and infections decrease drug metabolism capacity in human and experimental animals. In this study, I reported that NF-κB activation by LPS and TNF-α plays a pivotal role in the suppression of CYP3A4 through interactions of NF-κB with PXR/RXR complex. Inhibition of NF-κB by NF-κB specific suppressor SRIκBα reversed the suppressive effects of LPS and TNF-α. Furthermore, I showed that NF-κB p65 disrupted the association of PXR/RXRα complex with DNA sequences as determined by EMSA and chromatin immunoprecipitation assays. NF-κB p65 directly interacted with DNA binding domain of RXRα and DNA binding domain, hinge domain and ligand-binding domain of PXR and may prevent its binding to the consensus DNA sequences, thus inhibiting the transactivation by PXR/RXRα complex. This mechanism of suppression by NF-κB activation may be extended to other nuclear receptor-regulated systems where RXRα is a dimerization partner. Many genes regulated by PXR and AhR are important for phase I, II and III drug metabolism. In this study I reported a crosstalk between PXR and AhR pathways. AhR physically and functionally interacted with PXR and enhanced the PXR transcriptional activity, and the interaction repressed the AhR transcriptional activity. AhR also physically interacted with RXRα. The synergistic induction of Gsta1 in the liver of mice by PCN and TCDD might assume a different mechanism. The results suggested the metabolism kinetics of mixture drugs was different from and more complicated than that of single compound. Using a HepG2 cell-based PXR-driven CYP3A4-Luciferase assay, I reported that E/F domain of PXR was responsible for ligand-dependant activation. A/B domain was necessary for co-activating the ligand-dependent activation and D domain was suppressive. High doses of Valerian Root extraction were PXR-dependent CYP3A4 inducers. Green tea polyphenols, aflatoxin B1, CuSO4 and MnCl2 enhanced the PXR transcription activity activated by rifampicin. The results suggested PXR-mediated drug metabolism kinetics altered on xenobiotic exposure. Advisors/Committee Members: Tian, Yanan (advisor), Donnelly, Kirby C. (committee member), Porter, Weston W. (committee member), Safe, Stephen H. (committee member).

Subjects/Keywords: cytochrome P450 3A4; Pregnane X Receptor

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APA (6^th Edition):

Gu, X. (2009). Regulation of cytochrome P450 3A4 gene expression through modulating pregnane X receptor transcriptional activity by NF-ꢬ aryl hydrocarbon receptor and xenobiotics. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/ETD-TAMU-1630

Chicago Manual of Style (16^th Edition):

Gu, Xinsheng. “Regulation of cytochrome P450 3A4 gene expression through modulating pregnane X receptor transcriptional activity by NF-ꢬ aryl hydrocarbon receptor and xenobiotics.” 2009. Doctoral Dissertation, Texas A&M University. Accessed January 22, 2021. http://hdl.handle.net/1969.1/ETD-TAMU-1630.

MLA Handbook (7^th Edition):

Gu, Xinsheng. “Regulation of cytochrome P450 3A4 gene expression through modulating pregnane X receptor transcriptional activity by NF-ꢬ aryl hydrocarbon receptor and xenobiotics.” 2009. Web. 22 Jan 2021.

Vancouver:

Gu X. Regulation of cytochrome P450 3A4 gene expression through modulating pregnane X receptor transcriptional activity by NF-ꢬ aryl hydrocarbon receptor and xenobiotics. [Internet] [Doctoral dissertation]. Texas A&M University; 2009. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-1630.

Council of Science Editors:

Gu X. Regulation of cytochrome P450 3A4 gene expression through modulating pregnane X receptor transcriptional activity by NF-ꢬ aryl hydrocarbon receptor and xenobiotics. [Doctoral Dissertation]. Texas A&M University; 2009. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-1630

Texas A&M University

11. Kim, Moon Koo. Stable carbon isotope ratio of polycyclic aromatic hydrocarbons (PAHs) in the environment: validation of isolation and stable carbon isotope analysis methods.

Degree: PhD, Oceanography, 2004, Texas A&M University

URL: http://hdl.handle.net/1969.1/1099

► Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous, toxic contaminants that are released to the environment from various petrogenic and pyrogenic sources. In an effort to more… (more)

▼ Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous, toxic contaminants that are released to the environment from various petrogenic and pyrogenic sources. In an effort to more clearly identify and trace sources of PAHs in the environment, purification and compound specific isotope analysis methods were developed to accurately measure the stable carbon isotope ratio of individual PAHs. Development of the method included improving accuracy and precision of the isotopic measurement by producing highly pure extracts using various chromatographic techniques. The method was refined by improving compound separations using purification techniques and high resolution chromatographic columns. The purification method consists of alumina/silica gel column chromatography, gel permeation chromatography and thin layer chromatography. The mean recovery of PAHs after the purification procedure was approximately 80 %. Sample purities after purification were verified by GC/FID and full scan mass spectrometry. To better resolve peaks and provide more accurate stable carbon isotope measurements, various gas chromatographic conditions were evaluated. The precision of the method ranged between 0.08 and 0.43 . The analytical protocols were evaluated to confirm compositional and stable isotopic integrity during purification and stable isotopic analysis. To confirm the utility of the purification and isotope analysis methods, various environmental samples from marine, land and lacustrine environments were analyzed. The isolates were analyzed for the composition and the stable carbon isotope ratios of PAHs. The stable carbon isotope ratio was measured by GC/IRMS and the results, along with quantitative compound compositions, were used to characterize and identify the contaminant sources. The sources of the PAHs in the study areas were differentiated by PAH molecular ratios and confirmed by stable carbon isotope ratios. This study confirms that compound specific isotope analysis of pollutants by GC/IRMS can be used to identify PAH sources in environmental samples. The study also confirms that the purification and stable carbon isotope analysis methods that were developed can be used to accurately measure the stable carbon isotope ratios of PAHs in environmental samples for the purpose of source identification. GC/IRMS measurement of stable isotopic compositions can be an effective fingerprinting method when used in conjunction with traditional molecular composition methods. Advisors/Committee Members: Kennicutt, Mahlon C., II (advisor), Donnelly, Kirby C. (committee member), Cifuentes, Luis A. (committee member), Qian, Yaorong (committee member).

Subjects/Keywords: PAHs; stable carbon isotope ratio; source identification; compound specific isotope analysis

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APA (6^th Edition):

Kim, M. K. (2004). Stable carbon isotope ratio of polycyclic aromatic hydrocarbons (PAHs) in the environment: validation of isolation and stable carbon isotope analysis methods. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/1099

Chicago Manual of Style (16^th Edition):

Kim, Moon Koo. “Stable carbon isotope ratio of polycyclic aromatic hydrocarbons (PAHs) in the environment: validation of isolation and stable carbon isotope analysis methods.” 2004. Doctoral Dissertation, Texas A&M University. Accessed January 22, 2021. http://hdl.handle.net/1969.1/1099.

MLA Handbook (7^th Edition):

Kim, Moon Koo. “Stable carbon isotope ratio of polycyclic aromatic hydrocarbons (PAHs) in the environment: validation of isolation and stable carbon isotope analysis methods.” 2004. Web. 22 Jan 2021.

Vancouver:

Kim MK. Stable carbon isotope ratio of polycyclic aromatic hydrocarbons (PAHs) in the environment: validation of isolation and stable carbon isotope analysis methods. [Internet] [Doctoral dissertation]. Texas A&M University; 2004. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1969.1/1099.

Council of Science Editors:

Kim MK. Stable carbon isotope ratio of polycyclic aromatic hydrocarbons (PAHs) in the environment: validation of isolation and stable carbon isotope analysis methods. [Doctoral Dissertation]. Texas A&M University; 2004. Available from: http://hdl.handle.net/1969.1/1099

Texas A&M University

12. Avila, Luis Antonio de. Imazethapyr: red rice control and resistance, and environmental fate.

Degree: PhD, Agronomy, 2005, Texas A&M University

URL: http://hdl.handle.net/1969.1/2511

► Imazethapyr was recently approved for use in rice, but limited information is available regarding its efficacy, environmental fate or potential red rice resistance. Therefore, experiments… (more)

▼ Imazethapyr was recently approved for use in rice, but limited information is available regarding its efficacy, environmental fate or potential red rice resistance. Therefore, experiments were conducted to 1) determine the effect of flooding time, and stage of imazethapyr application in red rice control, 2) assess the acetolactate synthase resistance to imazethapyr on red rice ecotypes, 3) determine the relative photolysis of imazethapyr, and 4) determine the effect of soil and moisture on imazethapyr adsorption and availability. When imazethapyr was applied in sequential application of PRE followed by a POST application, to achieve >95% red rice control, flood needed to be established within 14 DAT when imazethapyr was applied EPOST, and 7 DAT when imazethapyr was applied LPOST. Delaying the flood up to 21 DAT reduced rice grain yield for both EPOST and LPOST application timings. Based on enzymatic activity, the mean I50 values were 1.5, 1.1, 1.5, 1.6, 20.8, and 590.6 mM of imazethapyr, respectively, for LA 5, MS 5, TX 4, ??Cypress??, ??CL-121??, and ??CL-161??. CL-161 was 32 times more resistant than CL-121, and at least 420 times more resistant than the average of the red rice ecotypes and ??Cypress??. Results from the ALS assay showed that red rice ecotypes and Cypress had high susceptibility to imazethapyr when compared with the tolerant CL-121 and the resistant CL-161. Measurable enzymatic tolerance to ALS-inhibiting herbicides has not yet developed in these red rice ecotypes. Imazethapyr quantum yield (fI ) was 0.023 ?? 0.002 while the hydroxyl radical rate constant ( I OH k?? ) was 2.8 ?? 0.44 x 1013 M-1 h-1. These results show that imazethapyr is susceptible to both direct and indirect photolysis. The results also show that imazethapyr photolysis in paddy water will be affected by turbidity due to its impact on the availability of sunlight to drive direct and indirect photolysis reactions. Imazethapyr was more available and more concentrated in sandy soil. With higher amounts of water in soil there was greater amount of imazethapyr in soil solution and a lower concentration of herbicide due to dilution. The double centrifuge method provided a better estimate of plant available herbicide. Advisors/Committee Members: Senseman, Scott A. (advisor), Chandler, James M. (committee member), Donnelly, Kirby C. (committee member), McCauley, Garry N. (committee member).

Subjects/Keywords: water management; ALS activity; tolerance; photolysis; red rice; Oryza sativa; adsorption; availability

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APA (6^th Edition):

Avila, L. A. d. (2005). Imazethapyr: red rice control and resistance, and environmental fate. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/2511

Chicago Manual of Style (16^th Edition):

Avila, Luis Antonio de. “Imazethapyr: red rice control and resistance, and environmental fate.” 2005. Doctoral Dissertation, Texas A&M University. Accessed January 22, 2021. http://hdl.handle.net/1969.1/2511.

MLA Handbook (7^th Edition):

Avila, Luis Antonio de. “Imazethapyr: red rice control and resistance, and environmental fate.” 2005. Web. 22 Jan 2021.

Vancouver:

Avila LAd. Imazethapyr: red rice control and resistance, and environmental fate. [Internet] [Doctoral dissertation]. Texas A&M University; 2005. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1969.1/2511.

Council of Science Editors:

Avila LAd. Imazethapyr: red rice control and resistance, and environmental fate. [Doctoral Dissertation]. Texas A&M University; 2005. Available from: http://hdl.handle.net/1969.1/2511

Texas A&M University

13. Lee, Jeong Eun. Mechanisms of aryl hydrocarbon receptor and estrogen receptor action in breast cancer cells.

Degree: PhD, Toxicology, 2006, Texas A&M University

URL: http://hdl.handle.net/1969.1/3109

► In MCF7 and T47D cells cotreated with 1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) plus 0.1-10 μM 3Â,4Â-dimethoxy flavone (DMF), there was a concentration-dependent decrease in the TCDD-induced… (more)

▼ In MCF7 and T47D cells cotreated with 1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) plus 0.1-10 μM 3Â,4Â-dimethoxy flavone (DMF), there was a concentration-dependent decrease in the TCDD-induced ethoxyresorufin O-deethylase (EROD) activity. Gel mobility shift assays showed that 3Â,4Â-DMF inhibited TCDD-induced aryl hydrocarbon receptor (AhR) transformation in rat liver cytosol and blocked TCDD-induced formation of the nuclear AhR complex in MCF7 and T47D cells. The antiestrogenic activity of TCDD in estrogen-induced transactivation assays in MCF7 cells was reversed by 3Â,4Â-DMF, confirming the AhR antagonist activity of this compound in breast cancer cells. Cotreatment of T47D and MCF7 cells with TCDD and 10 μM resveratrol inhibited induction of CYP1A1 mRNA and EROD activity. Resveratrol did not inhibit TCDD-induced AhR transformation and reporter gene activity. Actinomycin D chase experiments in T47D cells showed that the mechanism of inhibition of CYP1A1 mRNA and EROD activity is due to an increased rate of CYP1A1 mRNA degradation, suggesting that resveratrol inhibits CYP1A1 via an AhR-independent post-transcriptional pathway. Vitamin D receptor-interacting protein 150 (DRIP150) coactivated estrogen receptor α (ER α)-mediated transactivation and the response was AF2-dependent in ZR75 breast cancer cells. C-and N-terminal NR-boxes (amino acids 1186-1182 and 73-69, respectively) were not necessary for coactivation of ERα. Analysis of DRIP150 deletion mutants identified a 23 amino acid sequence (811-789) required for coactivation. The 23 amino acid contained two regions at amino acids 789-794 and 795-804 which resembled α-helical motifs identified in Lanuguinosa lipase/histamine N-methyl transferase and hepatocyte nuclear factor 1, respectively. A squelching assay using specific point mutations within each α-helix showed that the NIFSEVRVYN (795-804) region was the critical sequence required for the coactivator activity of DRIP150. Advisors/Committee Members: Safe, Stephen H. (advisor), Donnelly, Kirby C. (committee member), Burghardt, Robert C. (committee member), Phillips, Timothy D. (committee member).

Subjects/Keywords: 3' 4'-DMF; resveratrol; AhR; ER; DRIP150

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lee, J. E. (2006). Mechanisms of aryl hydrocarbon receptor and estrogen receptor action in breast cancer cells. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/3109

Chicago Manual of Style (16^th Edition):

Lee, Jeong Eun. “Mechanisms of aryl hydrocarbon receptor and estrogen receptor action in breast cancer cells.” 2006. Doctoral Dissertation, Texas A&M University. Accessed January 22, 2021. http://hdl.handle.net/1969.1/3109.

MLA Handbook (7^th Edition):

Lee, Jeong Eun. “Mechanisms of aryl hydrocarbon receptor and estrogen receptor action in breast cancer cells.” 2006. Web. 22 Jan 2021.

Vancouver:

Lee JE. Mechanisms of aryl hydrocarbon receptor and estrogen receptor action in breast cancer cells. [Internet] [Doctoral dissertation]. Texas A&M University; 2006. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1969.1/3109.

Council of Science Editors:

Lee JE. Mechanisms of aryl hydrocarbon receptor and estrogen receptor action in breast cancer cells. [Doctoral Dissertation]. Texas A&M University; 2006. Available from: http://hdl.handle.net/1969.1/3109

Texas A&M University

14. Afriyie-Gyawu, Evans. Safety and efficacy of NovaSil clay as a dietary supplement to prevent aflatoxicosis.

Degree: PhD, Toxicology, 2006, Texas A&M University

URL: http://hdl.handle.net/1969.1/3192

► It is well documented that aflatoxin contamination in foods presents significant economic and public health burdens worldwide. Aflatoxins, particularly aflatoxin B1 (AFB1), have been implicated… (more)

▼ It is well documented that aflatoxin contamination in foods presents significant economic and public health burdens worldwide. Aflatoxins, particularly aflatoxin B1 (AFB1), have been implicated in the etiology of disease and death in many parts of the world, necessitating research initiatives for intervention strategies designed to diminish biological exposure. Calcium montmorillonite clays (e.g. NovaSil Plus, NSP) have been found to tightly bind and inactivate aflatoxins in the gastrointestinal tract of multiple animal species. In the future, the hypothesis is that this strategy may also be appropriate for humans. Thus, the overall research goal was to investigate NSP suitability for human use through in vitro characterization followed by in vivo evaluation of NSP-AFB1 sorption and most importantly, safety of the clay. The first objective was to characterize the in vitro and in vivo sorption efficiency of NSP-AFB1 sorption and determine potential interactions with vitamin A (VA). Isothermal analysis suggested that NSP binds AFB1 with high capacity, affinity, and specificity in aqueous solution and further indicated that NSP does not appear to interact with VA. Subsequent short-term studies in Sprague-Dawley (S-D) rats and broiler chicks indicated that dietary inclusion of NSP (0.25%) significantly reduced AFB1 bioavailability without exerting overt toxicity. The second objective was to evaluate potential adverse effects of chronic ingestion of dietary NSP using male and female S-D rats in the absence of aflatoxins. Although statistically significant changes to a few parameters were noted, the differences did not appear to be NSP- or dose-dependent, suggesting that NSP at dietary inclusion levels as great as 2.0% (w/w) does not produce overt toxicity. Thus, this information increases the feasibility for using NSP in human trials in populations at high risk for aflatoxicosis. The third objective was to establish representative baseline data on human exposure to aflatoxins by collecting and quantifying urinary AFM1 in volunteers living in four separate communities in Ejura district of Ghana. Results revealed that urinary AFM1 in the study population was substantially high (mean = 1,850.86 Â± 274.59 pg/mg creatinine), indicating that this particular population was highly exposed to aflatoxins and could be used for future intervention trials. Advisors/Committee Members: Phillips, Timothy D. (advisor), Price, Ed. C. (committee member), Donnelly, Kirby C. (committee member), Kubena, Leon F. (committee member).

Subjects/Keywords: Aflatoxins; prevention; NovaSil clay

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Afriyie-Gyawu, E. (2006). Safety and efficacy of NovaSil clay as a dietary supplement to prevent aflatoxicosis. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/3192

Chicago Manual of Style (16^th Edition):

Afriyie-Gyawu, Evans. “Safety and efficacy of NovaSil clay as a dietary supplement to prevent aflatoxicosis.” 2006. Doctoral Dissertation, Texas A&M University. Accessed January 22, 2021. http://hdl.handle.net/1969.1/3192.

MLA Handbook (7^th Edition):

Afriyie-Gyawu, Evans. “Safety and efficacy of NovaSil clay as a dietary supplement to prevent aflatoxicosis.” 2006. Web. 22 Jan 2021.

Vancouver:

Afriyie-Gyawu E. Safety and efficacy of NovaSil clay as a dietary supplement to prevent aflatoxicosis. [Internet] [Doctoral dissertation]. Texas A&M University; 2006. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1969.1/3192.

Council of Science Editors:

Afriyie-Gyawu E. Safety and efficacy of NovaSil clay as a dietary supplement to prevent aflatoxicosis. [Doctoral Dissertation]. Texas A&M University; 2006. Available from: http://hdl.handle.net/1969.1/3192

Texas A&M University

15. Li, Xiangrong. Hormonal activation of genes through nongenomic pathways by estrogen and structurally diverse estrogenic compounds.

Degree: PhD, Toxicology, 2006, Texas A&M University

URL: http://hdl.handle.net/1969.1/3839

► Lactate dehydrogenase A (LDHA) is hormonally regulated in rodents, and increased expression of LDHA is observed during mammary gland tumorigenesis. The mechanisms of hormonal regulation… (more)

▼ Lactate dehydrogenase A (LDHA) is hormonally regulated in rodents, and increased expression of LDHA is observed during mammary gland tumorigenesis. The mechanisms of hormonal regulation of LDHA were investigated in breast cancer cells using a series of deletion and mutant reporter constructs derived from the rat LDHA gene promoter. Results of transient transfection studies showed that the -92 to -37 region of the LDHA promoter was important for basal and estrogen-induced transactivation, and mutation of the consensus CRE motif (-48/-41) within this region resulted in significant loss of basal activity and hormone-responsiveness. Gel mobility shift assays using nuclear extracts from MCF-7 cells indicated that CREB family proteins interacted with the CRE. Studies with kinase inhibitors showed that estrogen-induced activation of this CRE was dependent on protein kinase C, and these data show that LDHA is induced through a nongenomic (extranuclear) pathway of estrogen action. Estrogen activates several nongenomic pathways in MCF-7 cells, and this study investigated the effects of structurally diverse estrogenic compounds on activation of mitogen activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC), protein kinase A (PKA), and calcium/calmodulin-dependent protein kinase IV (CaMKIV). Activation of kinases was determined by specific substrate phosphorylation and transactivation assays that were diagnostic for individual kinases. The compounds investigated in this study include E2, diethylstilbestrol (DES), the phytoestrogen resveratrol, and the following synthetic xenoestrogens: bisphenol-A (BPA), nonylphenol, octylphenol, endosulfan, kepone, 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), and 2',3',4',5'-tetrachloro-4-biphenylol (HO-PCB-Cl4). With theexception of resveratrol, all the compounds activated PI3K and MAPK whereas activation of PKC by the xenoestrogens was structure-dependent and resveratrol, kepone and HO-PCB-Cl4 were inactive. Only minimal estrogen/xenoestrogen-dependent activation of PKA was observed. CaMKIV was activated only by E2 and DES, and HO-PCB-Cl4 was a potent inhibitor of CaMKIV-dependent activity. These results demonstrate that activation of nongenomic pathways by estrogenic compounds in MCF-7 cells is structure-dependent. Advisors/Committee Members: Safe, Stephen H. (advisor), Burghardt, Robert C. (committee member), Donnelly, Kirby C. (committee member), Porter, Weston W. (committee member).

Subjects/Keywords: estrogen; nongenomic pathways

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Li, X. (2006). Hormonal activation of genes through nongenomic pathways by estrogen and structurally diverse estrogenic compounds. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/3839

Chicago Manual of Style (16^th Edition):

Li, Xiangrong. “Hormonal activation of genes through nongenomic pathways by estrogen and structurally diverse estrogenic compounds.” 2006. Doctoral Dissertation, Texas A&M University. Accessed January 22, 2021. http://hdl.handle.net/1969.1/3839.

MLA Handbook (7^th Edition):

Li, Xiangrong. “Hormonal activation of genes through nongenomic pathways by estrogen and structurally diverse estrogenic compounds.” 2006. Web. 22 Jan 2021.

Vancouver:

Li X. Hormonal activation of genes through nongenomic pathways by estrogen and structurally diverse estrogenic compounds. [Internet] [Doctoral dissertation]. Texas A&M University; 2006. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1969.1/3839.

Council of Science Editors:

Li X. Hormonal activation of genes through nongenomic pathways by estrogen and structurally diverse estrogenic compounds. [Doctoral Dissertation]. Texas A&M University; 2006. Available from: http://hdl.handle.net/1969.1/3839

Texas A&M University

16. Roh, Hyung Keun. Deciphering Active Estrogen-Degrading Microorganisms in Bioreactors.

Degree: PhD, Civil Engineering, 2010, Texas A&M University

URL: http://hdl.handle.net/1969.1/ETD-TAMU-2009-08-7149

► Estrogens are a group of endocrine disrupting compounds capable of causing abnormalities in the reproductive systems of the wildlife. Wastewater is a major source of… (more)

▼ Estrogens are a group of endocrine disrupting compounds capable of causing abnormalities in the reproductive systems of the wildlife. Wastewater is a major source of environmental estrogens, in part due to incomplete removal of estrogens in biological wastewater treatment processes. This dissertation investigated factors affecting estrogen biodegradation in bioreactors. Specifically, research efforts were placed on characterization of several bacterial estrogen degraders (model strains: Aminobacter strains KC6 and KC7, and a Sphingomonas strain KC8) and examination of the effects of operating parameters on estrogen removal and estrogen-degrading microbial community structure. Sphingomonas strain KC8 can use 17beta-estradiol as a sole carbon source, suggesting that estrogen degradation by KC8 is a growth-linked, metabolic reaction; however, estrogen degradation by strains KC6 and KC7 might be a non-growth linked, cometabolic reaction. One important finding was that strain KC8 can also degrade and further utilize testosterone as a growth substrate. Strain KC8 was characterized in terms of its utilization kinetics toward estrogens and testosterone with the results that showed relatively smaller kinetic parameters than the typical values for heterotrophs in activated sludge. Strain KC8 can also grow on other organic constituents (glucose, succinate, and acetate). Strain KC8 retained its ability to degrade both 17beta-estradiol and estrone (after 15 d of growth on a complex nutrient medium without 17beta-estradiol). Effective removals (>98.7 %) of 17beta-estradiol with no significant differences were observed in sequencing batch reactors (SBRs) under three solid retention times (SRTs of 5, 10, 20 d). The population ratios of known estrogen degraders (strains KC8 and ammonia-oxidizing bacteria (AOB)) and amoA gene (associated with ammonia oxidation) to total bacteria decreased as SRT increased in SBRs. These observations correspond to the decreasing percentages of 17 beta-estradiol biodegraded in SBR when SRT increased from 5 to 20 d, when the sorption of 17 beta-estradiol onto biomass was considered. Real-time terminal restriction fragment length polymorphism showed that more ribotypes were observed in SBR-20d than SBR-5d. The species evenness (E) in microbial community structures in SBRs was not affected by SRT. However, diversity indices (Shannon-Weaver diversity index (H) and the reciprocal of Simpson?s index (1/D)) suggest that longer SRTs might lead to a more diverse microbial community structure. Advisors/Committee Members: Chu, Kung-Hui (advisor), Autenrieth, Robin L. (committee member), Wood, Thomas K. (committee member), Donnelly, Kirby C. (committee member).

Subjects/Keywords: Estrogen-degradation; Characterization of estrogen degraders; Sphingomonas strain KC8; Application of estrogendegraders in bioreactors

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Roh, H. K. (2010). Deciphering Active Estrogen-Degrading Microorganisms in Bioreactors. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/ETD-TAMU-2009-08-7149

Chicago Manual of Style (16^th Edition):

Roh, Hyung Keun. “Deciphering Active Estrogen-Degrading Microorganisms in Bioreactors.” 2010. Doctoral Dissertation, Texas A&M University. Accessed January 22, 2021. http://hdl.handle.net/1969.1/ETD-TAMU-2009-08-7149.

MLA Handbook (7^th Edition):

Roh, Hyung Keun. “Deciphering Active Estrogen-Degrading Microorganisms in Bioreactors.” 2010. Web. 22 Jan 2021.

Vancouver:

Roh HK. Deciphering Active Estrogen-Degrading Microorganisms in Bioreactors. [Internet] [Doctoral dissertation]. Texas A&M University; 2010. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2009-08-7149.

Council of Science Editors:

Roh HK. Deciphering Active Estrogen-Degrading Microorganisms in Bioreactors. [Doctoral Dissertation]. Texas A&M University; 2010. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2009-08-7149

Texas A&M University

17. Dimitriou-Christidis, Petros. Modeling the biodegradability and physicochemical properties of polycyclic aromatic hydrocarbons.

Degree: PhD, Civil Engineering, 2006, Texas A&M University

URL: http://hdl.handle.net/1969.1/4290

► The biodegradability and physicochemical properties of unsubstituted and methylated polycyclic aromatic hydrocarbons (PAHs) were investigated. The focus was on the development of models expressing the… (more)

▼ The biodegradability and physicochemical properties of unsubstituted and methylated polycyclic aromatic hydrocarbons (PAHs) were investigated. The focus was on the development of models expressing the influence of molecular structure and properties on observed behavior. Linear free energy relationships (LFERs) were developed for the estimation of aqueous solubilities, octanol/water partition coefficients, and vapor pressures as functions of chromatographic retention time. LFERs were tested in the estimation of physicochemical properties for twenty methylated naphthalenes containing up to four methyl substituents. It was determined that LFERs can accurately estimate physicochemical properties for methylated naphthalenes. Twenty unsubstituted and methylated PAHs containing up to four aromatic rings were biodegraded individually by Sphingomonas paucimobilis strain EPA505, and Monod-type kinetic coefficients were estimated for each PAH using the integral method. Estimated extant kinetic parameters included the maximal specific biodegradation rate, the affinity coefficient, and the inhibition coefficient. The generic Andrews model adequately simulated kinetic data. The ability of PAHs to serve as sole energy and carbon sources was also evaluated. Quantitative structure-biodegradability relationships (QSBRs) were developed based on the estimates of the kinetic and growth parameters. A genetic algorithm was used for QSBR development. Statistical analysis and validation demonstrated the predictive value of the QSBRs. Spatial and topological molecular descriptors were essential in explaining biodegradability. Mechanistic interpretation of the kinetic data and the QSBRs provided evidence that simple or facilitated diffusion through the cell membranes is the rate-determining step in PAH biodegradation by strain EPA505. A kinetic experiment was conducted to investigate biodegradation of PAH mixtures by strain EPA505. The investigation focused on 2-methylphenanthrene, fluoranthene, and pyrene, and their mixtures. Integrated material balance equations describing different interaction types were fitted to the depletion data and evaluated on a statistical and probabilistic basis. Mixture degradation was most adequately described by a pure competitive interaction model with mutual substrate exclusivity, a fully predictive model utilizing parameters estimated in the sole-PAH experiments only. The models developed in this research provide insight into how molecular structure and properties influence physicochemical properties and biodegradability of PAHs. The models have considerable predictive value and could reduce the need for laboratory testing. Advisors/Committee Members: Robin, Autenrieth L. (advisor), Batchelor, Bill (committee member), Donnelly, Kirby C. (committee member), McDonald, Thomas J. (committee member).

Subjects/Keywords: PAHs; QSAR; physicochemical properties; biodegradation kinetics; Sphingomonas paucimobilis EPA505

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dimitriou-Christidis, P. (2006). Modeling the biodegradability and physicochemical properties of polycyclic aromatic hydrocarbons. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/4290

Chicago Manual of Style (16^th Edition):

Dimitriou-Christidis, Petros. “Modeling the biodegradability and physicochemical properties of polycyclic aromatic hydrocarbons.” 2006. Doctoral Dissertation, Texas A&M University. Accessed January 22, 2021. http://hdl.handle.net/1969.1/4290.

MLA Handbook (7^th Edition):

Dimitriou-Christidis, Petros. “Modeling the biodegradability and physicochemical properties of polycyclic aromatic hydrocarbons.” 2006. Web. 22 Jan 2021.

Vancouver:

Dimitriou-Christidis P. Modeling the biodegradability and physicochemical properties of polycyclic aromatic hydrocarbons. [Internet] [Doctoral dissertation]. Texas A&M University; 2006. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1969.1/4290.

Council of Science Editors:

Dimitriou-Christidis P. Modeling the biodegradability and physicochemical properties of polycyclic aromatic hydrocarbons. [Doctoral Dissertation]. Texas A&M University; 2006. Available from: http://hdl.handle.net/1969.1/4290

Texas A&M University

18. Yang, Wonsuk. The bipyridyl herbicide paraquat-induced toxicity in human neuroblastoma SH-SY5Y cells: relevance to dopaminergic pathogenesis.

Degree: PhD, Toxicology, 2006, Texas A&M University

URL: http://hdl.handle.net/1969.1/4384

► Paraquat (PQ) is a cationic non-selective bipyridyl herbicide widely used in agriculture to control weeds and grasses. Epidemiologic studies indicate that exposure to pesticides can… (more)

▼ Paraquat (PQ) is a cationic non-selective bipyridyl herbicide widely used in agriculture to control weeds and grasses. Epidemiologic studies indicate that exposure to pesticides can be a risk factor in the incidence of Parkinson`s disease (PD). A strong correlation has been reported between exposure to paraquat and PD incidence in Canada, Taiwan, and United States. This correlation is supported by animal studies showing that paraquat produces toxicity in dopaminergic neurons of the rat and mouse brain. However, it is unclear how paraquat triggers toxicity in dopaminergic neurons. Based on the previous reports, it was hypothesized that paraquat may induce oxidative stress and proteasomal dysfunction-mediated toxicity in dopaminergic neurons. To explore this possibility, dopaminergic SH-SY5Y human neuroblastoma cells were treated with paraquat, and several biomarkers of oxidative stress or proteasomal dysfunction were investigated. First, a specific dopamine transporter inhibitor GBR12909 significantly protected SY5Y cells against the toxicity of paraquat, indicating that paraquat exerts its toxicity by a mechanism involving the dopamine transporter (DAT). Second, paraquat increased the levels of reactive oxygen species (ROS) in SY5Y cells, but decreased the levels of glutathione. Third, paraquat inhibited glutathione peroxidase activity, but did not affect glutathione reductase activity. On the other hand, paraquat increased GST activity by 24 hr, after which GST activity returned to the control value at 48 hr. Fourth, paraquat decreased mitochondrial transmembrane potential (MTP). Fifth, paraquat produced the increases in malondialdehyde (MDA) and protein carbonyls, as well as DNA fragmentation, indicating oxidative damage to major cellular components. Sixth, paraquat decreased proteasomal activity, the activities of mitochondrial complex I and V, and intracellular ATP levels, but increased the activities of caspase 3 and 9, indicating that proteasomal inhibition is linked to mitochondrial dysfunction accompanied by the activation of apoptotic signaling pathway. Seventh, paraquat increased the protein levels of heme oxygenase-1 (HO-1), p53, Bax, ÃÂ±-synuclein and ubiquitinated proteins. Eighth, paraquat induced nuclear condensation. Taken together, these findings support the hypothesis that paraquat produces oxidative stress and proteasomal dysfunctionmediated toxicity in SY5Y cells. Thus, current findings suggest that paraquat may induce the pathogenesis of dopaminergic neurons through oxidative stress and proteasomal dysfunction. Advisors/Committee Members: Tiffany-Castiglioni, Evelyn (advisor), Donnelly, Kirby C. (committee member), Miranda, Rajesh C. (committee member), Welsh, Jane C. (committee member).

Subjects/Keywords: paraquat; dopaminergic pathogenesis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Yang, W. (2006). The bipyridyl herbicide paraquat-induced toxicity in human neuroblastoma SH-SY5Y cells: relevance to dopaminergic pathogenesis. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/4384

Chicago Manual of Style (16^th Edition):

Yang, Wonsuk. “The bipyridyl herbicide paraquat-induced toxicity in human neuroblastoma SH-SY5Y cells: relevance to dopaminergic pathogenesis.” 2006. Doctoral Dissertation, Texas A&M University. Accessed January 22, 2021. http://hdl.handle.net/1969.1/4384.

MLA Handbook (7^th Edition):

Yang, Wonsuk. “The bipyridyl herbicide paraquat-induced toxicity in human neuroblastoma SH-SY5Y cells: relevance to dopaminergic pathogenesis.” 2006. Web. 22 Jan 2021.

Vancouver:

Yang W. The bipyridyl herbicide paraquat-induced toxicity in human neuroblastoma SH-SY5Y cells: relevance to dopaminergic pathogenesis. [Internet] [Doctoral dissertation]. Texas A&M University; 2006. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1969.1/4384.

Council of Science Editors:

Yang W. The bipyridyl herbicide paraquat-induced toxicity in human neuroblastoma SH-SY5Y cells: relevance to dopaminergic pathogenesis. [Doctoral Dissertation]. Texas A&M University; 2006. Available from: http://hdl.handle.net/1969.1/4384

Texas A&M University

19. Bellum, Sairam. Neurotoxic mechanisms of methylmercury: cellular and behavior changes.

Degree: PhD, Toxicology, 2007, Texas A&M University

URL: http://hdl.handle.net/1969.1/4992

► The organic or methylated form of mercury (Hg), consisting of one methyl group bound to each atom of Hg, (methylmercury; MeHg), accounts for most of… (more)

▼ The organic or methylated form of mercury (Hg), consisting of one methyl group bound to each atom of Hg, (methylmercury; MeHg), accounts for most of the Hg to which humans are exposed. MeHg, by virtue of its lipophilicity is highly neurotoxic to both the developing and mature central nervous system (CNS). Historically, MeHg has been implicated in high morbidity and mortality rates over the last 40 years in Japan, Iraq, Pakistan and Guatemala. The most common symptom exhibited in these exposure episodes was cerebellar ataxia. Recent in vitro studies using cultured granule cells showed that MeHg alters intracellular calcium ion ([Ca2+]i) homeostasis, potentiates reactive oxygen species (ROS) generation and loss of mitochondrial membrane potential leading to apoptotic death of cerebellar granule neurons. To better understand the neurotoxic mechanisms of MeHg on cerebellum, changes with respect to biochemical processes in cerebellar granule cells and associated behavior changes were investigated. The aims of this dissertation were: (1) to assess mercury concentrations in mouse brain using different routes of administration and different tissue preparations, (2) to determine the behavior effects of in vivo MeHg exposure in young adult mice. (3) to understand specific biochemical processes leading to granule cell death/dysfunction due to in vivo MeHg toxicity in mice, and (4) to determine the toxic effects of in vivo MeHg exposure on mice aged between 16-20 months. The present results showed that repeated oral exposure to MeHg results in greater accumulation of Hg in brain tissue when compared to single oral or subcutaneous exposures at the same concentration of MeHg. Behavior analysis revealed that MeHg at the concentrations used in this study had profound effects on motor coordination and balance in young adult and aged mice. Investigation of biochemical processes in cerebellar granule cells of mice exposed to MeHg showed an increase in ROS generation, alteration of ([Ca2+]i (in young adult mice) and loss of MMP in young adult and aged mice. However, these changes did not lead to apoptotic cell death of granule cells at the concentrations of MeHg used and at the specific time point it was investigated in young adult mice. Advisors/Committee Members: Abbott, Louise C (advisor), Donnelly, Kirby C (committee member), Phillips, Timothy D (committee member), Stoica, Gheorghe (committee member).

Subjects/Keywords: Methylmercury; Neurotoxicity; Cerebellum; In vivo

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bellum, S. (2007). Neurotoxic mechanisms of methylmercury: cellular and behavior changes. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/4992

Chicago Manual of Style (16^th Edition):

Bellum, Sairam. “Neurotoxic mechanisms of methylmercury: cellular and behavior changes.” 2007. Doctoral Dissertation, Texas A&M University. Accessed January 22, 2021. http://hdl.handle.net/1969.1/4992.

MLA Handbook (7^th Edition):

Bellum, Sairam. “Neurotoxic mechanisms of methylmercury: cellular and behavior changes.” 2007. Web. 22 Jan 2021.

Vancouver:

Bellum S. Neurotoxic mechanisms of methylmercury: cellular and behavior changes. [Internet] [Doctoral dissertation]. Texas A&M University; 2007. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1969.1/4992.

Council of Science Editors:

Bellum S. Neurotoxic mechanisms of methylmercury: cellular and behavior changes. [Doctoral Dissertation]. Texas A&M University; 2007. Available from: http://hdl.handle.net/1969.1/4992

Texas A&M University

20. Dash, Bhagirathi. Molecular cloning and characterization of important stress and redox regulatory genes from Hydra vulgaris.

Degree: PhD, Toxicology, 2007, Texas A&M University

URL: http://hdl.handle.net/1969.1/4994

► In this research, important stress and redox regulatory genes present in Hydra vulgaris were isolated and characterized to facilitate our understanding of the evolution and… (more)

▼ In this research, important stress and redox regulatory genes present in Hydra vulgaris were isolated and characterized to facilitate our understanding of the evolution and mechanisms of stress response. H. vulgaris heat shock protein 70 (HvHSP70), extracellular copper zinc superoxide dismutase (HvECCuZnSOD), manganese superoxide dismutase (HvMnSOD), phospholipid peroxidase glutathione peroxidase (HvPHGPx) and monofunctional catalase (HvCatalase) were cloned and characterized with regard to stress response, phylogeny and molecular structure. The HSP70 gene isolated from H. vulgaris encodes a polypeptide of 650 amino acids (Mw=710,037) and is interrupted by three intron sequences. The 5' non-coding region of the HvHSP70 possessed the canonical heat shock elements. Phylogenetically HvHSP70 formed a distinct lineage. A molecular model generated for the N-terminal fragment of the HvHSP70 displayed the heat shock protein fold and domains of phosphotransferases. The EC-CuZnSOD cDNA isolated from H. vulgaris encodes a protein of 189 amino acids (Mw=20959.73); the first 19 amino acids constitute the presumed signal peptide. Phylogenetically HvEC-CuZnSOD is grouped with ECCuZnSODs from several organisms. A molecular model generated for the HvEC-CuZnSOD displayed the CuZnSOD (beta)-barrel fold. The MnSOD cDNA isolated from H. vulgaris encodes a protein of 219 amino acids (Mw=24348.75); the first 21 amino acids constitute the presumed mitochondria-targeting signal peptide. Phylogenetically HvMnSOD is clustered with mollusk and crustacean MnSODs. A molecular model generated for the HvMnSOD displayed the N-terminal long alpha antiparallel hairpin and the Cterminal mixed alpha/beta fold characteristic of MnSODs. The PHGPx gene isolated from H. vulgaris encodes a polypeptide of 168 amino acids (Mw=18746.51) including a TGA-encoded selenocysteine at residue 44 and lacks any intron. Phylogenetically HvPHGPx is grouped with PHGPxs from several organisms. A molecular model generated for the HvPHGPx displayed the thioredoxin fold. The 3'-end of a cDNA sequence encoding for 168 amino acids of the Cterminal end of a catalase was isolated from H. vulgaris. Phylogenetically HvCatalase is grouped with heme-containing monofunctional catalases. Hydrae exposed to thermal, starvation, oxidative and metal stress responded by regulating respective mRNA transcriptions suggesting that these genes are involved in stress and (anti)oxidative processes and may have potential as molecular biomarkers for assessing aquatic environment quality. Advisors/Committee Members: Phillips, Timothy D. (advisor), Donnelly, Kirby C. (committee member), Loeppert, Richard H. (committee member), Safe, Stephen H. (committee member).

Subjects/Keywords: Stress genes; Redox regulatory genes; Hydra vulgaris

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dash, B. (2007). Molecular cloning and characterization of important stress and redox regulatory genes from Hydra vulgaris. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/4994

Chicago Manual of Style (16^th Edition):

Dash, Bhagirathi. “Molecular cloning and characterization of important stress and redox regulatory genes from Hydra vulgaris.” 2007. Doctoral Dissertation, Texas A&M University. Accessed January 22, 2021. http://hdl.handle.net/1969.1/4994.

MLA Handbook (7^th Edition):

Dash, Bhagirathi. “Molecular cloning and characterization of important stress and redox regulatory genes from Hydra vulgaris.” 2007. Web. 22 Jan 2021.

Vancouver:

Dash B. Molecular cloning and characterization of important stress and redox regulatory genes from Hydra vulgaris. [Internet] [Doctoral dissertation]. Texas A&M University; 2007. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1969.1/4994.

Council of Science Editors:

Dash B. Molecular cloning and characterization of important stress and redox regulatory genes from Hydra vulgaris. [Doctoral Dissertation]. Texas A&M University; 2007. Available from: http://hdl.handle.net/1969.1/4994

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