title: Cyclobutane pyrimidine dimers are predominant DNA lesions in whole human skin exposed to UVA radiation.
abstract: Solar UV radiation is the most important environmental factor involved in the pathogenesis of skin cancers. The well known genotoxic properties of UVB radiation (290-320 nm) mostly involve bipyrimidine DNA photoproducts. In contrast, the contribution of more-abundant UVA radiation (320-400 nm) that are not directly absorbed by DNA remains poorly understood in skin. Using a highly accurate and quantitative assay based on HPLC coupled with tandem mass spectrometry, we determined the type and the yield of formation of DNA damage in whole human skin exposed to UVB or UVA. Cyclobutane pyrimidine dimers, a typical UVB-induced DNA damage, were found to be produced in significant yield also in whole human skin exposed to UVA through a mechanism different from that triggered by UVB. Moreover, the latter class of photoproducts is produced in a larger amount than 8-oxo-7,8-dihydro-2'-deoxyguanosine, the most common oxidatively generated lesion, in human skin. Strikingly, the rate of removal of UVA-generated cyclobutane pyrimidine dimers was lower than those produced by UVB irradiation of skin. Finally, we compared the formation yields of DNA damage in whole skin with those determined in primary cultures of keratinocytes isolated from the same donors. We thus showed that human skin efficiently protects against UVB-induced DNA lesions, whereas very weak protection is afforded against UVA. These observations emphasize the likely role played by the UVA-induced DNA damage in skin carcinogenesis and should have consequences for photoprotection strategies.
authors.affiliation: Commissariat à l'Energie Atomique (CEA)/La Direction des Sciences de la Matière (DSM)/Département de Recherche Fondamentale sur la Matière Condensée, Service de Chimie Inorganique et Biologique UMR-E 3 (CEA-UJF), CEA-Grenoble, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Mouret
authors.forename: Caroline
authors.initials: C
authors.lastname: Baudouin
authors.forename: Marie
authors.initials: M
authors.lastname: Charveron
authors.forename: Alain
authors.initials: A
authors.lastname: Favier
authors.forename: Jean
authors.initials: J
authors.lastname: Cadet
authors.forename: Thierry
authors.initials: T
authors.lastname: Douki
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D002478:Cells, Cultured; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D006801:Humans; D011740:Pyrimidine Dimers / Q000032:analysis / Q000378:metabolism*; D012867:Skin / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects*; D014466:Ultraviolet Rays
chemical_list: D011740:Pyrimidine Dimers; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine