title: Oxidatively generated base damage to cellular DNA by hydroxyl radical and one-electron oxidants: similarities and differences.
abstract: Hydroxyl radical (OH) and one-electron oxidants that may be endogenously formed through oxidative metabolism, phagocytosis, inflammation and pathological conditions constitute the main sources of oxidatively generated damage to cellular DNA. It is worth mentioning that exposure of cells to exogenous physical agents (UV light, high intensity UV laser, ionizing radiation) and chemicals may also induce oxidatively generated damage to DNA. Emphasis is placed in this short review article on the mechanistic aspects of OH and one-electron oxidant-mediated formation of single and more complex damage (tandem lesions, intra- and interstrand cross-links, DNA-protein cross-links) in cellular DNA arising from one radical hit. This concerns DNA modifications that have been accurately measured using suitable analytical methods such as high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. Evidence is provided that OH and one-electron oxidants after generating neutral radicals and base radical cations respectively may partly induce common degradation pathways. In addition, selective oxidative reactions giving rise to specific degradation products of OH and one-electron oxidation reactions that can be used as representative biomarkers of these oxidants have been identified.
authors.affiliation: Institut Nanosciences et Cryogénie, CEA/Grenoble, F-38054 Grenoble Cedex 9, France; Département de Médecine Nucléaire et Radiobiologie, Faculté de Médecine des Sciences de la santé, Université de Sherbrooke, Sherbrooke, Québec J1H 5N4, Canada. Electronic address: jean.cadet@cea.fr.
authors.forename: Jean
authors.initials: J
authors.lastname: Cadet
authors.affiliation: Département de Médecine Nucléaire et Radiobiologie, Faculté de Médecine des Sciences de la santé, Université de Sherbrooke, Sherbrooke, Québec J1H 5N4, Canada.
authors.forename: J Richard
authors.initials: JR
authors.lastname: Wagner
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D004583:Electrons; D017665:Hydroxyl Radical / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D016877:Oxidants; D017665:Hydroxyl Radical
keywords: Clustered DNA damage; DNA–protein cross-links; Interstrand cross-links; Intrastrand cross-links; Oxidized nucleobases; Radical cations; Tandem base lesions