Role of DNA repair in mutagenesis of Chinese hamster ovary cells by 7-bromomethylbenz[a]anthracene.
- 1 January 1982
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 79 (2) , 534-538
- https://doi.org/10.1073/pnas.79.2.534
Abstract
The role of DNA repair in mutagenesis was studied in normal, repair-proficient Chinese hamster ovary cells and in 2 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 induction at 3 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. The dose-response curve for mutations was essentially linear in the repair-deficient cells. In the normal cells 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 efficiency of inducing ouabain-resistant mutations in the repair-deficient 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, was induced with greater efficiency in the repair-deficient cells. [The role of DNA repair in carcinogenesis is discussed.].This publication has 30 references indexed in Scilit:
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