Mutagenic specificity of solar UV light in nucleotide excision repair-deficient rodent cells.
To investigate the role of nucleotide excision repair (NER) in the cellular processing of carcinogenic DNA photoproducts induced by defined, environmentally relevant portions of the solar wavelength spectrum, we 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 phosphoribosyltransferase (aprt) locus in NER-deficient (ERCC1) Chinese hamster ovary (CHO) cells. The frequency distributions of mutational classes induced by UVB and by simulated sunlight in repair-deficient CHO cells were virtually identical, each showing a marked increase in tandem CC-->TT transitions relative to NER-proficient cells. A striking increase in CC-->TT events was also previously documented for mutated p53 tumor-suppressor 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 cultured rodent cells irradiated with artificial solar light generates the same distinctive "fingerprint" for sunlight mutagenesis as the p53 locus in NER-deficient humans exposed to natural sunlight in vivo. Moreover, in strong contrast to the situation for repair-component CHO cells, where a significant role for UVA was previously noted, the mutagenic specificity of simulated sunlight in NER-deficient CHO cells and of natural sunlight in humans afflicted with xeroderma pigmentosum can be entirely accounted for by the UVB portion of the solar wavelength spectrum.
Sage
E
E
Section de Biologie, Institute Curie, Paris, France.
Lamolet
B
B
Brulay
E
E
Moustacchi
E
E
Chteauneuf
A
A
Drobetsky
E A
EA
D000228:Adenine Phosphoribosyltransferase / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D008969:Molecular Sequence Data; D016296:Mutagenesis; D017354:Point Mutation; D014466:Ultraviolet Rays
D000228:Adenine Phosphoribosyltransferase