Mechanisms of DNA Oxidation

Abstract

Oxidative damage of DNA caused by a variety of chemical and physical agents appears to be linked to cancer. However, it is becoming increasingly clear that endogenous generation of oxidants, such as hydroxyl radical and peroxynitrite, lead to oxidation of DNA, and this may cause cancer in individuals where no obvious exposure to chemical or physical agents known to be carcinogenic has occurred. The mechanisms for generation of these two oxidants in living organisms will be discussed and their reactivities with DNA to produce oxidized products (e.g., 8-oxo-dG) will be presented with special emphasis on the individual characteristics of the generation and reactivity of each oxidant.

Adult Motor Neuron Apoptosis Is Mediated by Nitric Oxide and Fas Death Receptor Linked by DNA Damage and p53 Activation

“…Ϫ , induce DNA damage (Aust and Eveleigh, 1999). The precursors of ONOO Ϫ , NO and superoxide anion (Beckman, 1990), by themselves are not aggressively genotoxic.…”

Products of Thymine Oxygenation by a Non-heme Oxygenation Model, Fe^II(MeCN)₆²⁺–Ac₂O–H₂O₂, and the Transition State Model between Oxoiron and Thymine

“…[1][2][3] In particular, HO radical has been shown to be generated in aqueous solutions by ionizing radiation, 4,5) UV irradiation, 6) and Fenton-catalyzed Haber-Weiss-type reactions (Fenton reaction). 7,8) In order to elucidate the mechanism and oxidative products, therefore, Fenton reactions with DNA and DNA bases, pirimidines and purines, have been powerfully carried out by many scientists using Fenton-like biomimetic oxygenation models, such as m-chloroperbenzoic acid (MCPBA), 9 12) and OsO 4 .…”

“…Detection of urinary thymine glycol has been suggested as a measure of oxidative damage to DNA in humans and animals. 1,2,7) The release of thymine glycol and thymidine glycol from damaged DNA has been shown to take place via DNA repair by thymine glycol glycosylase and excision repair, respectively 17,18) ; however, the mechanisms by which thymine glycol is formed from OH radicals in the oxidative damage of DNA are not fully understood.…”

Clinical practices in neonatal oxygenation: where have we failed? What can we do?

“…About 2% of the oxygen consumed by humans produces reactive oxygen species (ROS). 4 If the production of hydroxyl radical and peroxynitrite exceeds the catabolism, oxidative damage to DNA appears, leading to a variety of diseases.…”