Abstract
Ultraviolet light (UV) in the sunlight induces skin cancers. Although the UVB component of the solar UV is known as a major contributor for the skin carcinogenesis, the relative importance of the longer wavelength component UVA has not been determined clearly. Since in vitro studies showed that UVA induces oxidative damage like 8-hydroxy-2'-deoxyguanine (8-OH-dG) in cellular DNA, some relevance of the UVA-mediated oxidative stress has been insisted. To clarify this point, we studied an in vivo mutation spectrum in skin induced by a monochromatic UVA light within the UVA1 range (340-400 nm), using a laser emitting a highly intense 364-nm beam. LacZ-transgenic mice developed for mutation research were exposed to the 364-nm light from an Ar-ion laser irradiator (National Institute for Basic Biology, Okazaki, Japan) at the intensity of 300 W/m2. Dose-dependent induction of 8-OH-dG and cyclobutane pyrimidine dimers (CPD) were observed in the skin genome. The mutant frequency of the transgene also increased along with the irradiation dose. The induced mutation spectrum in the exposed epidermis was determined: more than 90% of the mutations were base substitutions, and 70% of them were C -> T transitions, 90% of which occurred at dipyrimidine sites. Oxidative stress-specific G -> T transversions were only recovered at a background level. These results indicate that genotoxic effect of UVA1 is mainly mediated through formation of CPD, not through oxidative DNA damage produced with the UVA-mediated oxidative stress. (This study was carried out under the NIBB Cooperative Research Program for the Okazaki Large Spectrograph; 4-507, 5-507, 6-511 and 7-509.)
