A correlation between mutagenic and carcinogenic potencies in a diverse group of N-nitrosamines: Determination of mutagenic activities of weakly mutagenic N-nitrosamines

The mutagenic activities of a diverse group of N-nitrosamines were measured in Salmonella typhimurium TA 100 under conditions designed to maximize metabolism of N-nitrosamines and enhance their mutagenic effects. These conditions were also chosen since some of the carcinogens were previously reported to be non-mutagenk or of questionable mutagenic activity and some only became mutagenic after the bacteria were exposed to a "threshold dose" of metabolites. The mutagenic potencies spanned a range of 10⁵-fold and correlated well with semiquantitative carcinogenic potencies taken from the literature. This correlation appears to be the strongest yet reported for any particular class of compounds. In addition, the mutagenic activities of a number of carcinogens, previously reported to be non-mutagenk, were determined. Among the structural features necessary for high mutagenic activity in this group of compounds was a potential, unsubstituted methylating or ethylating group. Substitution of alkyI, hydroxyl, methoxyl, and cyano moieties at the α or β carbon of these groups reduced mutagenic activity.