Mutagenicity of N-Nitroso Bile Acid Conjugates in Salmonella typhimurium and Diploid Human Lymphoblasts¹

Two N-nitroso bile acid conjugates, N-nitrosotaurocholic acid and N-nitrosoglycocholic acid, were tested for mutagenicity by forward mutation assay in Salmonella typhimurium TM 677 and in diploid human lymphoblasts, line TK6. N-Nitrosoglycocholic acid and N-nitrosotaurocholic acid showed similar concentration-response curves in the bacterial assay with statistically significant mutant fractions observed at about 0.12 mm. Non-nitrosated parent compounds were nonmutagenic. However, in the human cell assay, N-nitrosotaurocholic acid gave statistically significant mutant fractions only at 0.4 mm, but N-nitrosoglycocholic acid was mutagenic at 0.05 µm, some 9000 times more potent. Experiments with quantitative Ames' S. typhimurium reversion assays indicated mutagenesis via base substitution.