The mutational specificity of simulated sunlight at the aprt locus in rodent cells

Abstract

To elucidate the nature of sunlight mutagenesis in mammalian cells, the mutational specificity of simulated solar light (SSL) has been established at the Chinese hamster ovary adenine phosphoribosyltransferase (aprt) locus. Among a collection of 36 independent SSL-induced mutations, the majority were single or tandem double C-->T transitions at dipyrimidine sites. This is consistent with previous investigations of 254 nm UVC on the aprt gene, as well as on various other genetic targets from diverse species, and supports a pre-eminent role for cyclobutane dimers and/or (6-4) photoproducts in solar mutagenesis. However, some substantial differences were also noted in the frequency and distribution of mutational classes generated by SSL versus UVC at the aprt locus. In particular, a reduction in the proportion of SSL-induced C-->T transitions was accompanied by significant increases in the incidence of T-->G transversions (25% versus 6%, P < 0.05) and of tandem double CC-->TT events at mutational hotspots (25% versus 9%, P < 0.05). Furthermore, a much greater fraction of SSL-induced mutations could be attributed to photoproducts on the non-transcribed strand of the aprt gene than was observed following treatment with 254 nm UV (94% versus 64%, P < 0.002). The general significance of these disparities between SSL and UVC mutagenesis at the aprt locus remains to be established, underscoring the need for further investigations on the effects of solar light in mammalian cells.