Role of DNA repair in mutagenesis by 7-bromomethylbenz(a)anthracer (mutagen sensitivity/mutation induction/sister chromatid exchange/t

The role of DNA repair in mutagenesis was stud- ied in normal, repair-proficient Chinese hamster ovary cells and in two mutant strains that are deficient in excision repair. By using the mutagen 7-bromomethylbenz(a)anthracene (7-BrMeBA) and the technique of alkaline elution of DNA, the mutants were found to be defective at or before the incision step of excision repair. Dose-responses were determined for cell killing, mutation induc- tion at three loci, and sister chromatid exchanges over a survival range of 1.0-0.1 after 7-BrMeBA treatment. The mutants were 5-fold more sensitive to killing than were the normal cells, but the degree of hypersensitivity to mutation induction varied depending on the mutant strain, the genetic marker, and the dose of mutagen. In each instance, the dose-response curve for mutations was es- sentially linear in the repair-deficient cells. In the normal cells, however, the curves for induced resistance to thioguanine and azaadenine were complex and were curvilinear with increasing slope at low doses. This behavior may be attributable to saturation of the excision repair system. No difference was seen in the ef- ficiency of inducing ouabain-resistant mutations in the repair-de- ficient cells compared to the normal cells, indicating a qualitatively different behavior of this marker. These results are consistent with excision repair of 7-BrMeBA damage being error-free in Chinese hamster ovary cells. Sister chromatid exchange, another manifestation of DNA damage, also.was induced with greater ef- ficiency in the repair-deficient cells.