Mutagenicity of nitrosated cimetidines

Dinitrosocimetidine and mononitrosocimetidine were tested in a series of short term assay systems. Both compounds were mutagenic in the absence of rat liver microsomes. The dinitrosocimetidine produced higher mutagenic or clastogenic effects at concentrations that were 50 to 500 times lower than the concentrations at which the mononitrosocimetidine produces its maximum effects. The most sensitive short term assay system was the Chinese hamster ovary cell culture system. Dinitrosocimetidine caused sister chromatid exchanges at a concentration of 10(-8) M and chromosome aberrations at 10(-7) M in this system. Dinitrosocimetidine had moderate activity in the bacterial short term assay systems. In the Ames test, strain TA 100 was the most sensitive. The compound was of lower activity in the E. coli WP-2 and the E. coli rec- systems.