DNA Base Damage by Reactive Oxygen Species, Oxidizing Agents, and UV Radiation

Emphasis has been placed in this article dedicated to DNA damage on recent aspects of the formation and measurement of oxidatively generated damage in cellular DNA in order to provide a comprehensive and updated survey.This includes single pyrimidine and purine base lesions, intrastrand cross-links, purine 5 0 ,8-cyclonucleosides, DNA-protein adducts and interstrand cross-links formed by the reactions of either the nucleobases or the 2-deoxyribose moiety with the hydroxyl radical, one-electron oxidants, singlet oxygen, and hypochlorous acid.In addition, recent information concerning the mechanisms of formation, individual measurement, and repair-rate assessment of bipyrimidine photoproducts in isolated cells and human skin upon exposure to UVB radiation, UVA photons, or solar simulated light is critically reviewed.I n this article, we emphasize recent develop- ments in the formation of damage to cellular DNA mediated by reactive oxygen species (ROS) and oxidizing agents, including singlet oxygen, the hydroxyl radical ( † OH), one-electron oxidants, hypochlorous acid (HOCl), and ten-eleven translocation (TET) oxygenases involved in epigenetic regulation.These advances have been possible because of the development of sensitive and powerful high-performance liquid chromatography-mass spectrometry (HPLC-MS)/ mass spectrometry (MS) methods allowing one to revise previously reported data obtained using methods such as gas chromatographymass spectrometry (GC-MS), immunoassays, and HPLC with single MS detection (Cadet et al. 2011(Cadet et al. , 2012a)).Considerable progress has also been made in the elucidation of oxidative degradation pathways of isolated DNA and related model compounds (for recent comprehensive reviews, see Gimisis and Cismas ¸2006;Neeley and Essigmann 2006;Pratviel and Meunier 2006;von Sonntag 2006;Cadet et al. 2008Cadet et al. , 2010 Cadet et al. , 2012b;;Dedon 2008;Burrows 2009;Wagner and Cadet 2010).In addition, there is much complementary information on solar-radiation-induced formation of bipyrimidine photoproducts in the DNA of fibroblasts, keratinocytes, and human skin.In particular, the distribution of UVA and UVB photoproducts has been determined, allowing accurate determination of their rates of repair (Cadet et al. 2009(Cadet et al. , 2012c)).