title: Repair of the three main types of bipyrimidine DNA photoproducts in human keratinocytes exposed to UVB and UVA radiations.
abstract: Induction of DNA damage by solar UV radiation is a key event in the development of skin cancers. Bipyrimidine photoproducts, including cyclobutane pyrimidine dimers (CPDs), (6-4) photoproducts (64 PPs) and their Dewar valence isomers, have been identified as major UV-induced DNA lesions. In order to identify the predominant and most persistent lesions, we studied the repair of the three types of photolesions in primary cultures of human keratinocytes. Specific and quantitative data were obtained using HPLC associated with tandem mass spectrometry. As shown in other cell types, 64 PPs are removed from UVB-irradiated keratinocytes much more efficiently than CPDs. In contrast, CPDs are still present in high amounts when cells recover their proliferation capacities after cell cycle arrest and elimination of a part of the population by apoptosis. The predominance of CPDs is still maintained when keratinocytes are exposed to a combination of UVB and UVA. Under these conditions, 64 PPs are converted into their Dewar valence isomers that are as efficiently repaired as their (6-4) precursors. Exposure of cells to pure UVA radiation generates thymine cyclobutane dimers that are slightly less efficiently repaired than CPDs produced upon UVB irradiation. Altogether, our results show that CPDs are the most frequent and the less efficiently repaired bipyrimidine photoproducts irrespectively of the applied UV treatment.
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: Bruno
authors.initials: B
authors.lastname: Canguilhem
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: D017209:Apoptosis; D002478:Cells, Cultured; D004260:DNA Repair; D006801:Humans; D015603:Keratinocytes / Q000528:radiation effects*; D011740:Pyrimidine Dimers / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D011740:Pyrimidine Dimers