Characterization of a CHO variant in respect to alkylating agent-induced biological effects and DNA repair.
From the Chinese hamster ovary line CHO-9 a resistant variant, Cl 3, was isolated after treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Cl 3 cells were much more resistant to the cytotoxic effects of MNNG (D10 of 1.8 microgram/ml MNNG as compared to 0.23 microgram/ml for parental line) and other methylating N-nitroso compounds, but they had the same sensitivity to various other alkylating agents. MNNG was equally effective in sensitive parent line and resistant variant in inducing sister-chromatid exchanges (SCEs) and mutations to 6-thioguanine resistance. The increased resistance of Cl 3 was not due to reduced cellular uptake of MNNG, to a more efficient repair of methylated purine bases, or to differences in MNNG-induced inhibition of DNA synthesis. It is concluded that the resistant variant has some unknown tolerance mechanism which alters the cytotoxic, but not the SCE- and mutation-inducing effects of methylating N-nitroso compounds.
D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D006224:Cricetinae; D045647:DNA Glycosylases; D004260:DNA Repair; D004261:DNA Replication / Q000187:drug effects; D004351:Drug Resistance; D008745:Methylation; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D009603:Nitroso Compounds / Q000633:toxicity*; D012854:Sister Chromatid Exchange / Q000187:drug effects; D013379:Substrate Specificity
D000477:Alkylating Agents; D009603:Nitroso Compounds; D008769:Methylnitronitrosoguanidine; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases