Effects of secondary biliary acids on the mutagenicity of N-methyl-N'-nitro-N-nitrosoguanidine, 2-acetylaminofluorene and 2-nitrofluorene towards Salmonella typhimurium strains.

The two secondary biliary acids (lithocholic and deoxycholic acids) were co-mutagenic when they were each co-incubated with dimethylhydrazine in the presence of Salmonella typhimurium TA 100. These observations were extended to other toxic chemicals, acting as direct (N-methyl-N'nitro-N-nitrosoguanidine and 2-nitrofluorene) or indirect (2-acetylaminofluorene) mutagens. Lithocholic and deoxycholic acids show a similar behavior towards genotoxic molecules. Nevertheless two differences must be noted. Lithocholic acid was the stronger co-mutagen. When lithocholic acid inhibited mutagenic activity of 2-nitrofluorene, deoxycholic acid did not modify it. Interactions between the two secondary bile acids occurred so that the co-mutagenic activity of the mixture of these two bile acids depended on the ratio of their concentrations. Besides their cancer-promoting effect, biliary acids also could have co-initiating effect that could depend upon the ratio of their concentration in the intestine. Calculating the ratio of fecal concentrations of deoxycholic/lithocholic acids thus could be a more sensitive index for cancer risk than simply measuring the fecal concentration of the two biliary acids taken separately.