The use of DNA-repair-deficient mutants of Chinese hamster ovary cells in studying mutagenesis mechanisms and testing for environmental mutagens.
Our laboratory has taken a somatic-cell-genetics approach to the study of mutagenesis by utilizing mutant strains of Chinese hamster ovary (CHO) cells that are deficient in DNA repair processes. From more than 150 UV-sensitive strains tested, five complementation classes were identified, and representative mutants were found to be defective at, or before, the incision step of excision repair. A representative mutant, strain UV-5, was compared with the parental strain in terms of cytotoxicity and dose-response curves for mutation induction after treatment with UV and several chemicals that are known to produce large adducts in DNA. Excision repair in normal CHO cells protects against both cytotoxicity and mutagenesis, but the degree of protection depends on both the agent and the genetic marker used for detecting mutations. Upon treatment with low doses (100% cell survival) of the polyaromatic hydrocarbon 7-bromomethylbenz(a)anthracene, repair-deficient UV-5 cells had linear responses for mutation induction to thioguanine resistance or azaadenine resistance, whereas the normal repair-proficient cells showed curvilinear responses in which the slope increased with dose. This behavior suggests that in the normal cells the repair system acting on potentially mutagenic lesions becomes saturated at doses that produce cytotoxicity. In no instance was a lower mutation frequency induced in UV-5 cells than the parental cells, at a given dose of mutagen, suggesting that the excision repair system is error-free in normal CHO cells.
D000818:Animals; D001711:Biotransformation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D004260:DNA Repair; D004305:Dose-Response Relationship, Drug; D005260:Female; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000032:analysis*; D009154:Mutation; D010053:Ovary; D014466:Ultraviolet Rays
D009153:Mutagens