title: Bipyrimidine photoproducts rather than oxidative lesions are the main type of DNA damage involved in the genotoxic effect of solar UVA radiation.
abstract: Exposure to solar UV radiation gives rise to mutations that may lead to skin cancer. UVA (320-340 nm) constitutes the large majority of solar UV radiation but is less effective than UVB (290-320 nm) at damaging DNA. Although UVA has been implicated in photocarcinogenesis, its contribution to sunlight mutagenesis has not been elucidated, and DNA damage produced by UVA remains poorly characterized. We employed HPLC-MS/MS and alkaline agarose gel electrophoresis in conjunction with the use of specific DNA repair proteins to determine the distribution of the various classes and types of DNA lesions, including bipyrimidine photoproducts, in Chinese hamster ovary cells exposed to pure UVA radiation, as well as UVB and simulated sunlight (lambda > 295 nm) for comparison. At UVA doses compatible with human exposure, oxidative DNA lesions are not the major type of damage induced by UVA. Indeed, single-strand breaks, oxidized pyrimidines, oxidized purines (essentially 8-oxo-7,8-dihydroguanine), and cyclobutane pyrimidine dimers (CPDs) are formed in a 1:1:3:10 ratio. In addition, we demonstrate that, in contrast to UVB and sunlight, UVA generates CPDs with a large predominance of TT CPDs, which strongly suggests that they are formed via a photosensitized triplet energy transfer. Moreover, UVA induces neither (6-4) photoproducts nor their Dewar isomers via direct absorption. We also show that UVA photons contained in sunlight, rather than UVB, are implicated in the photoisomerization of (6-4) photoproducts, a quickly repaired damage, into poorly repaired and highly mutagenic Dewar photoproducts. Altogether, our data shed new light on the deleterious effect of UVA.
authors.affiliation: Laboratoire Lésions des Acides Nucléiques, Service de Chimie Inorganique et Biologique & CNRS FRE 2600, CEA/DSM/Département de Recherche Fondamentale sur la Matière Condensée, CEA Grenoble, F-38054 Grenoble Cedex 9, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Douki
authors.forename: Anne
authors.initials: A
authors.lastname: Reynaud-Angelin
authors.forename: Jean
authors.initials: J
authors.lastname: Cadet
authors.forename: Evelyne
authors.initials: E
authors.lastname: Sage
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003503:Cyclobutanes / Q000737:chemistry / Q000528:radiation effects; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000528:radiation effects; D004249:DNA Damage; D007536:Isomerism; D016296:Mutagenesis; D010084:Oxidation-Reduction / Q000528:radiation effects; D017785:Photons; D011740:Pyrimidine Dimers / Q000737:chemistry / Q000235:genetics* / Q000528:radiation effects*; D013472:Sunlight / Q000009:adverse effects*; D013941:Thymine / Q000737:chemistry / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D003503:Cyclobutanes; D011740:Pyrimidine Dimers; D004247:DNA; D013941:Thymine