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.

The dark side of melanin exposed: Sun worshippers may have more to worry about than the DNA damage that occurs while they're relaxing on the beach. It seems that the DNA photoproducts responsible for cancer-causing mutations in skin cells continue to be generated for hours after sunlight exposure. Premi et al. find that a key mediator of this delayed damage is melanin, a pigment thought to protect against cancer (see the Perspective by Taylor). They propose a “chemiexcitation” model in which reactive oxygen and nitrogen species induced by ultraviolet light excite an electron in melanin fragments. This energy is then transferred to DNA, inducing the same damage as ultraviolet light, but in the dark. Conceivably, this energy could be dissipated by adding quenchers to sunscreens. Science , this issue p. 842 ; see also p. 824