Cyclobutane pyrimidine dimers are predominant DNA lesions in whole human skin exposed to UVA radiation

S. Mouret (1) , C. Baudouin (2) , M. Charveron (2) , A. Favier (1) , J. Cadet (1) , Thierry Douki (3)

1 LAN - Laboratoire Lésions des Acides Nucléiques
2 Centre de R&D Pierre Fabre - Centre de Recherche Pierre Fabre
3 SYMMES - SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé

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 carcinogen-esis and should have consequences for photoprotection strategies.

Domaines: Biochimie [q-bio.BM]

S. Mouret, C. Baudouin, M. Charveron, A. Favier, J. Cadet, et al.. Cyclobutane pyrimidine dimers are predominant DNA lesions in whole human skin exposed to UVA radiation. Proceedings of the National Academy of Sciences of the United States of America, 2006, 103 (37), pp.13765-13770. ⟨hal-01966814⟩