Experimental models for the biological detection of N-nitroso compounds formed from amines and nitrite

The secondary and tertiary amines morpholine, aminopyrine and cimetidine as well as their nitroso products were examined for mutagenicity with the Ames Salmonella typhimurium microsome test (strains TA1535 and TA100) and the host-mediated assay. The formation of mutagenic nitroso compounds from morpholine and aminopyrine in the presence of nitrite could be demonstrated in artificial gastric juice and was confirmed in the stomach of mice in vivo. In contrast, the positive response of the chemical nitrosation in vitro with cimetidine did not match with the mammalian host-mediated assay results. To enhance sensitivity the role of modifiers of nitrosation, such as ascorbic acid and thiocyanate as well as the influence of biotransformation were studied.