Potent mutagenic potential of 4-methylquinoline: metabolic and mechanistic considerations.

4-Methylquinoline (4-MeQ) showed an extraordinarily potent mutagenicity when compared to quinoline and isomeric methylquinolines. The major metabolite of 4-MeQ was 4-hydroxymethylquinoline, which was not mutagenic under the assay condition employed. Deuteration of the methyl group of 4-MeQ resulted in a decrease in the amount of the hydroxymethyl metabolite and an increase in mutagenicity, indicating that hydroxylation of the substituent methyl group is a detoxication process. A 3-chloro derivative of 4-MeQ was proven to be non-mutagenic. 4-Ethyl-quinoline, as well as 4-hydroxymethylquinoline, was much less mutagenic than 4-MeQ. Taking account of the structure-mutagenicity relationship, a possible mechanism is proposed for the potent mutagenic potential of 4-MeQ.