Mutagenicity of alpha-hydroxy N-nitrosamines in V79 Chinese hamster cells.
N-Nitrosodialkylamines are activated metabolically by alpha-hydroxylation. Chemical properties and bacterial mutagenicity of alpha-hydroxy N-nitrosamines have been reported previously. This paper describes potent and direct mutagenicity of four N-nitroso-N-(hydroxymethyl)alkylamines in V79 Chinese hamster cells, using ouabain resistance as an indicator. The mutagenic potency depended on the alkyl group, decreasing in the following order: methyl greater than ethyl greater than propyl, butyl. A similar order was observed for cytotoxicity. Mutagenic and cytotoxic potencies of these alpha-hydroxy N-nitrosamines in V79 cells were well correlated not only with those of model compounds (alpha-acetoxy and alpha-hydroperoxy N-nitrosamines), but also with their alkylating ability, measured by alkylation of thiophenol. The mutagenic activity of the alpha-hydroxy N-nitrosamines in V79 cells was shown to be parallel to that in Salmonella typhimurium TA1535 and to that of N-nitrosodialkylamines in V79 cells, after metabolic activation by rat hepatocytes. The results obtained here further support the conclusion that the alpha-hydroxy N-nitrosamine is the active species in the metabolic activation of carcinogenic and mutagenic N-nitrosodialkylamines.
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D009152:Mutagenicity Tests; D009153:Mutagens; D009602:Nitrosamines / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
D009153:Mutagens; D009602:Nitrosamines