title: Larger yield of cyclobutane dimers than 8-oxo-7,8-dihydroguanine in the DNA of UVA-irradiated human skin cells.
abstract: Exposure to solar ultraviolet light is the major cause of most skin cancers. While the genotoxic properties of UVB radiation are now well understood, the DNA damaging processes triggered by less energetic but more abundant UVA photons remain to be elucidated. Evidence has been provided for the induction of oxidative lesions to cellular DNA including strand breaks and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo). Formation of cyclobutane pyrimidine dimers (CPDs) has also been reported, mostly in rodent cells. In order to gain insights into the relevance of the latter photoproducts in UVA-mutagenesis of human skin, we quantified the level of 8-oxodGuo and CPDs within primary cultures of normal fibroblasts and keratinocytes using specific chromatographic assays. The yield of formation of CPDs was found to be higher than that of 8-oxodGuo in both cell types. In addition, CPDs were mostly TT derivatives, and neither (6-4) photoproducts nor Dewar valence isomers were detected. These observations are reminiscent of results obtained in rodent cells and suggest that a photosensitized triplet energy transfer occurs and that this reaction is more efficient than photooxidation of DNA components. The predominant formation of CPDs with respect to oxidative damage within normal human skin cells exposed to UVA radiation should be taken into account in photoprotection strategies.
authors.affiliation: Laboratoire Lésions des Acides Nucléiques, Service de Chimie Inorganique et Biologique, CEA/DSM/Département de Recherche Fondamentale sur la Matière Condensée, CEA-Grenoble, 17, avenue des Martyrs, 38054 Grenoble Cedex 9, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Courdavault
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 / Q000031:analogs & derivatives; D004247:DNA / Q000737:chemistry / Q000528:radiation effects*; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis*; D006801:Humans; D066298:In Vitro Techniques; D011740:Pyrimidine Dimers / Q000032:analysis*; D012867:Skin / Q000737:chemistry / Q000528:radiation effects*; D014466:Ultraviolet Rays
chemical_list: D011740:Pyrimidine Dimers; D006147:Guanine; C078307:8-oxo-7,8-dihydrodeoxyguanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA