Analysis of mutation induced in UV-irradiated skin

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It is important to develop an efficient and simple method for evaluation of the frequency of sunlight-induced mutation in mammalian skin because the recent increase of the ultraviolet light (UV) component of sunlight has caused significant induction of human skin carcinoma. Utilizing a bacterial lacZ gene-introduced transgenic mouse Muta^<TM>, which has been widely used for in vivo assay of induced mutations in an animal body exposed to various mutagens, we studied the induced mutations in mouse dorsal skin irradiated with three kinds of UV sources ; UVB, UVA and solar UV.We showed each source could increase efficiently and dose-dependently the frequency of the lacZ mutants in skin genome. DNA sequence changes in the lacZ gene of the mutants recovered from the irradiated skin were analyzed, and the UV-specific mutations of G : C to A : T at dipyrimidine sites were found in more than 80% of the mutant clones irrespective of the UV sources. We also detected CC to TT tandem base substitutions, which has been considered as the most representative mutation signifying UV exposure, with all UV sources. These results indicate that the animal system introduced here will be useful for the quantitative risk evaluation of skin cancer with the sunlight exposure of human skin.