Mutagenicity of alpha-hydroxy N-nitrosamines in V79 Chinese hamster cells.
Carcinogenic and mutagenic N-nitrosodialkylamines are metabolically activated through alpha-hydroxylation. The synthesis, chemical properties, and microbial mutagenicity of alpha-hydroxy N-nitrosamines have been reported previously. Potent mutagenicity of four N-nitroso-N-(hydroxymethyl)-alkylamines (alkyl = methyl, ethyl, propyl, and butyl) was demonstrated in the present study in V79 Chinese hamster cells, ouabain resistance being used as an indicator. All the compounds were strong mutagens in the absence of metabolic activation systems. The mutagenic and cytotoxic potencies correlated well with each other, and depended on the alkyl group, decreasing in potency in the following order: methyl greater than ethyl greater than propyl = butyl. Their alkylating reactivity was measured by alkylation of thiophenol, and a good linear relationship was observed between the mutagenic and cytotoxic potencies and their alkylating reactivity. The mutagenic and cytotoxic potencies of the alpha-hydroxy N-nitrosamines in V79 cells were well correlated with those of alpha-acetoxy and alpha-hydroperoxy N-nitrosamines with respect to the effect of alkyl group. The results obtained here supported further that alpha-hydroxy N-nitrosamine is the active species in the metabolic activation of N-nitrosodialkylamine.
D000477:Alkylating Agents; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D006863:Hydrogen-Ion Concentration; D006900:Hydroxylation; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens; D009602:Nitrosamines / Q000633:toxicity*; D010636:Phenols; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds
D000477:Alkylating Agents; D009153:Mutagens; D009602:Nitrosamines; D010636:Phenols; D013438:Sulfhydryl Compounds; C042983:thiophenol