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1. Καλούδης, Παναγιώτης. Μελέτη προϊόντων οξειδωτικής καταστροφής του DNA.

Degree: 2009, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)

The genetic degeneration and instability of the human genome has been linked intimately with all aspects of maintenance of DNA integrity, which is a macromolecule constantly targeted by environmental and endogenous genotoxic agents. DNA appears to be a critical cellular target for the biological effects of oxidation processes mediated by various physical and chemical agents such as ionizing radiation, solar light, photosensitizers, and several enviromental carcinogens. The endogenous production of reactive oxygen species represents another source of oxidative stress for the cells, while the mechanisms for the production of oxidative DNA damage products have been thoroughly studied due to their paramount significance in a number of biological processes. The target of the present thesis was the synthesis and the radiolytic study of modified nucleosidic derivatives in an effort to determine the mechanisms involved in DNA damage. The main tools utilized in the aforementioned studies were the observation of the absorption spectra of the active intermediates through pulse radiolysis and their interpretation through theoretical calculations and characterization of the final stable products through γ-radiolysis experiments. The independent and site-specific generation of nucleosidic radicals on the sugar or the base moiety is a particularly useful tool for studying the radical mechanisms involved. We performed the synthesis of the photolabile derivatives 4.2 and 3.22, which under photolysis generate selectively the neutral radical of the one electron oxidized guanine without the simultaneous formation of the superoxide radical anion, and the C1΄ sugar radical of 2΄-deoxyadenosine, respectively. The opening of the cyclobutane ring of the cis-syn thymine dimer 2.3 was studied and a new mechanism was proposed for this process, which contradicts the widely accepted view of a chain radical mechanism. Moreover, the chemistry of the C5΄ radical of 2΄-deoxyadenosine (3.11), 2΄-deoxyinosine (3.14) and 2΄-deoxyguanosine (3.16) was also studied under various conditions, while the radiolytic study of 8-oxo-2΄-deoxyguanosine (4.1) and other 8-substituted purine nucleosides in the effort of elucidating the mechanisms involved were performed as well. Tautomerization of nucleosidic radicals was discovered recently in the one electron oxidized guanosine. With the purpose of finding new nucleosidic derivatives that exhibit radical tautomerization, as well as the specific characteristics that enable this process, 8-bromo-2-aminoadenosine (5.14), 8-bromoxanthosine (5.15) and 8-bromoisoguanosine (5.16) were synthesized and studied by radiolytic means. Indeed, it was found that reaction of 5.14 with hydrated electrons affords two tautomers, while the mechanism for the one electron reduction of 5.15 and 5.16 was determined. Finally, the one electron reduction of guanosine was reevaluated and the existence of two tautomeric forms of the one electron reduced guanine was discovered, while radiolytic studies of the reaction between…

Subjects/Keywords: Παλμική ραδιόλυση; γ - ραδιόλυση; Ριζική ταυτομέρεια νουκλεοζιτών; Ηλεκτρόνιο, Οξείδωση ενός; Ηλεκτρόνιο, Αναγωγή ενός; Φωτόλυση; Θεωρητικοί υπολογισμοί; Ocidative DNA damage; Pulse radiolysis; γ - radiolysis; Nucleosidic radical tautomerization; One electron oxidation; One electron rediction; Photolysis; Theoretical calculations

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APA (6th Edition):

Καλούδης, . . (2009). Μελέτη προϊόντων οξειδωτικής καταστροφής του DNA. (Thesis). National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Retrieved from http://hdl.handle.net/10442/hedi/19422

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):

Καλούδης, Παναγιώτης. “Μελέτη προϊόντων οξειδωτικής καταστροφής του DNA.” 2009. Thesis, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Accessed March 08, 2021. http://hdl.handle.net/10442/hedi/19422.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Καλούδης, Παναγιώτης. “Μελέτη προϊόντων οξειδωτικής καταστροφής του DNA.” 2009. Web. 08 Mar 2021.

Vancouver:

Καλούδης . Μελέτη προϊόντων οξειδωτικής καταστροφής του DNA. [Internet] [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2009. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/10442/hedi/19422.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Καλούδης . Μελέτη προϊόντων οξειδωτικής καταστροφής του DNA. [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2009. Available from: http://hdl.handle.net/10442/hedi/19422

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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