title: Formation and repair of oxidatively generated damage in cellular DNA.
abstract: In this review article, emphasis is placed on the critical survey of available data concerning modified nucleobase and 2-deoxyribose products that have been identified in cellular DNA following exposure to a wide variety of oxidizing species and agents including, hydroxyl radical, one-electron oxidants, singlet oxygen, hypochlorous acid and ten-eleven translocation enzymes. In addition, information is provided about the generation of secondary oxidation products of 8-oxo-7,8-dihydroguanine and nucleobase addition products with reactive aldehydes arising from the decomposition of lipid peroxides. It is worth noting that the different classes of oxidatively generated DNA damage that consist of single lesions, intra- and interstrand cross-links were unambiguously assigned and quantitatively detected on the basis of accurate measurements involving in most cases high performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry. The reported data clearly show that the frequency of DNA lesions generated upon severe oxidizing conditions, including exposure to ionizing radiation is low, at best a few modifications per 106normal bases. Application of accurate analytical measurement methods has also allowed the determination of repair kinetics of several well-defined lesions in cellular DNA that however concerns so far only a restricted number of cases.
authors.affiliation: Département de médecine nucléaire et radiobiologie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4. Electronic address: jean.cadet@usherbrooke.ca.
authors.forename: Jean
authors.initials: J
authors.lastname: Cadet
authors.affiliation: Leonard Davis School of Gerontology of the Ethel Percy Andrus Gerontology Center, The University of Southern California, Los Angeles, CA 90089-0191, United States; Division of Molecular & Computational Biology, Department of Biological Sciences of the Dornsife College of Letters, Arts, and Sciences, The University of Southern California, Los Angeles, CA 90089-0191, United States.
authors.forename: Kelvin J A
authors.initials: KJA
authors.lastname: Davies
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, CP 26077, CEP 05508 000 São Paulo, SP, Brazil.
authors.forename: Marisa Hg
authors.initials: MH
authors.lastname: Medeiros
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, CP 26077, CEP 05508 000 São Paulo, SP, Brazil.
authors.forename: Paolo
authors.initials: P
authors.lastname: Di Mascio
authors.affiliation: Département de médecine nucléaire et radiobiologie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4.
authors.forename: J Richard
authors.initials: JR
authors.lastname: Wagner
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts; D004249:DNA Damage; D004260:DNA Repair; D049308:Dioxygenases / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D018384:Oxidative Stress; D011839:Radiation, Ionizing; D017382:Reactive Oxygen Species / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D018736:DNA Adducts; D017382:Reactive Oxygen Species; D049308:Dioxygenases
keywords: DNA oxidative degradation pathways; Measurement of oxidatively generated DNA damage; Repair of oxidized bases; Single base oxidation modifications