Mutagenicity of N-nitroso bile acid conjugates in Salmonella typhimurium and diploid human lymphoblasts.
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. Nonnitrosated 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 microM, some 9000 times more potent. Experiments with quantitative Ames' S. typhimurium reversion assays indicated mutagenesis via base substitution.
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004171:Diploidy; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*; D009152:Mutagenicity Tests; D009154:Mutation; D009602:Nitrosamines / Q000009:adverse effects*; D012486:Salmonella typhimurium / Q000187:drug effects*
D009602:Nitrosamines; C034937:N-nitrosoglycocholic acid; C034936:N-nitrosotaurocholic acid