Mutagenicity and rat-liver S9 demethylation kinetics of N-nitrosomethylaniline and its ring-substituted derivatives.

N-nitrosomethylaniline, an esophageal carcinogen in the rat, was inactive in the Ames mutagenicity assay under all conditions examined. However, various ring-substituted N-nitrosomethylanilines were found to be mutagenic; some of these did not require activation. No correlation could be found between the rate of demethylation or substituent effects of the ring-substituted N-nitrosomethylanilines and mutagenic potency. The protein concentration and levels of aryl hydrocarbon hydroxylase in the liver S9 fraction were determined to be poor indices of the ability of S9 to activate nitrosamines to their mutagenic metabolites.