Relationships between specific DNA adducts, mutation, cell survival, and SCE formation.
The induction of biological responses and the formation of specific DNA adducts by 2 classes of carcinogens have been compared in CHO cells. The simple alkylating agents reacted with a variety of nucleophilic centers within DNA while the N-oxidized arylamines reacted only at C8 of deoxyguanosine. With the alkylating agents, mutation induction, which correlated strongly with 0(6)-alkylguanine levels, did not correlate well with either SCE frequency or cell survival. SCE formation correlated strongly with reduced cell survival but could not be related to the concentration of a single DNA adduct. Exposure of CHO cells to each of the 3 N-oxidized arylamines resulted in a single DNA adduct, substituted through the C8 of deoxyguanosine. When arylamine-induced biological responses were compared, the results were similar to those found with the alkylating agents. That is, mutation induction did not relate well with either SCE frequency or cell survival, although a close relationship was found between the latter 2 responses. These results suggest that both the site of substitution and the DNA adduct structure may be important in eliciting genotoxic responses. These results also suggest that the toxic and SCE-inducing effects of these 2 classes of carcinogens may be related.
D000818:Animals; D001560:Benzidines / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000378:metabolism*; D005260:Female; D005449:Fluorenes / Q000494:pharmacology; D009153:Mutagens / Q000494:pharmacology; D009154:Mutation; D010053:Ovary; D011721:Pyrenes / Q000494:pharmacology; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013329:Structure-Activity Relationship
D001560:Benzidines; D005449:Fluorenes; D009153:Mutagens; D011721:Pyrenes; C001368:N-hydroxy-2-aminofluorene; C045050:N-hydroxy-N'-acetylbenzidine; C044707:1-nitrosopyrene; D004247:DNA