| Abstract
| - Exposure to solar UV radiation gives rise to mutations that may lead to skin cancer. UVA(320−340 nm) constitutes the large majority of solar UV radiation but is less effective than UVB (290−320 nm) at damaging DNA. Although UVA has been implicated in photocarcinogenesis, its contributionto sunlight mutagenesis has not been elucidated, and DNA damage produced by UVA remains poorlycharacterized. We employed HPLC−MS/MS and alkaline agarose gel electrophoresis in conjunction withthe use of specific DNA repair proteins to determine the distribution of the various classes and types ofDNA lesions, including bipyrimidine photoproducts, in Chinese hamster ovary cells exposed to pure UVAradiation, as well as UVB and simulated sunlight (λ > 295 nm) for comparison. At UVA doses compatiblewith human exposure, oxidative DNA lesions are not the major type of damage induced by UVA. Indeed,single-strand breaks, oxidized pyrimidines, oxidized purines (essentially 8-oxo-7,8-dihydroguanine), andcyclobutane pyrimidine dimers (CPDs) are formed in a 1:1:3:10 ratio. In addition, we demonstrate that,in contrast to UVB and sunlight, UVA generates CPDs with a large predominance of TT CPDs, whichstrongly suggests that they are formed via a photosensitized triplet energy transfer. Moreover, UVA inducesneither (6−4) photoproducts nor their Dewar isomers via direct absorption. We also show that UVAphotons contained in sunlight, rather than UVB, are implicated in the photoisomerization of (6−4)photoproducts, a quickly repaired damage, into poorly repaired and highly mutagenic Dewar photoproducts.Altogether, our data shed new light on the deleterious effect of UVA.
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