MUTAGENIC SPECIFICITY OF SOLAR UV-LIGHT IN NUCLEOTIDE EXCISION REPAIR-DEFICIENT RODENT CELLS

To investigate the role of nucleotide excision repair (NER) in the cel lular processing of carcinogenic DNA photoproducts induced by defined, environmentally relevant portions of the solar wavelength spectrum, w e have determined the mutagenic specificity of simulated sunlight (310 -1100 nm), UVA (350-400 nm), and UVB (290-320 nm), as well as of the ' 'nonsolar'' model mutagen 254-nm UVC, at the adenine phosphoribosyltra nsferase (aprt) locus in NER-deficient (ERCCI) Chinese hamster ovary ( CHO) cells, The frequency distributions of mutational classes induced by UVB and by simulated sunlight in repair-deficient CAO cells were vi rtually identical, each showing a marked increase in tandem CC --> TT transitions relative to NER-proficient cells. A striking increase in C C --> TT events was also previously documented for mutated p53 tumor-s uppressor genes From nonmelanoma tumors of NER-deficient, skin cancer- prone xeroderma pigmentosum patients, compared to normal individuals, The data therefore indicate that the aprt gene in NER-deficient cultur ed rodent cells irradiated with artificial solar light generates the s ame distinctive ''fingerprint'' for sunlight mutagenesis as the p53 lo cus in NER-deficient humans exposed to natural sunlight in vivo. Moreo ver, in strong contrast to the situation for repair-competent CHO cell s, where a significant role for UVA was previously noted, the mutageni c specificity of simulated sunlight in NER-deficient CHO cells and of natural sunlight in humans afflicted with xeroderma pigmentosum can he entirely accounted for by the UVB portion of the solar wavelength spe ctrum.