Effect of lithocholic acid on the mutagenicity of some substituted aromatic amines.

The effects of lithocholic acid on the mutagenicity of 24 aromatic amines in the Ames assay were examined. When lithocholic acid was added to the Salmonella/mammalian--microsome mutagenicity system with the use of postmitochondrial supernatant fractions from livers of male inbred SD rats pretreated with Aroclor 1254 or phenobarbital, various effects on the mutagenic responses were observed. The effects on mutagenicity varied with the substrate and the type of 9,000 X g-supernatant fraction. With preparations from phenobarbital-treated rats, lithocholic acid caused an inhibition of the mutagenic response with 16 of 24 compounds tested. The mutagenicity of three of these test compounds (2,4-diaminoanisole, 3-methoxy-4-aminoazobenzene, and 1-aminoanthracene) was unaffected by inclusion of lithocholic acid, while the lithocholic acid enhanced the mutagenicity of three others (2-aminoanthracene, 9-aminophenanthrene, and 2-acetylaminoanthracene). With 9,000 X g-supernatant fractions from Aroclor 1254-treated rats, the mutagenicity of eight test compounds was unaffected and that of 10 others was inhibited, while the mutagenicity of six others was enhanced when lithocholic acid was included in Ames assay mixtures. These results demonstrate that lithocholic acid can cause three distinct effects on the mutagenicity of these amines when included in these assays, namely, 1) no effect--no change in mutagenicity of the test compound, 2) inhibitory--levels of mutations significantly decreased or inhibited relative to those of controls, and 3) enhancement--significantly higher levels of mutations relative to those of controls. On the basis of structure alone and without detailed knowledge of the metabolism of each test compound, no conclusions or predictions could be made regarding the effects of lithocholic acid on the mutagenicity of these or any other compounds in the Ames assay.