Modification of Mutagenic Activities of Pro-Mutagens by Glyco-Ursodeoxycholic Acid in the Ames Assay

Abstract

Mutagenicity, co-mutagenicity and anti-mutagenicity of glyco-ursodeoxycholic acid (GUDCA) were examined by the Ames assay using Salmonella typhimurium strain TA98 with S9. As pro-mutagens, 2-aminoanthracene (2AA), Benzo[a]pyrene (BaP), 3-amino-1-dimethyl-5H-pyrido[4, 3-b]indole (Trp-P-2), 2-amino-3-methylimidazo[4, 5-f]quinoline (IQ) and 2-amino-3, 4-dimethylimidazo[4, 5-f]quinoline (MeIQ) were used. In addition to these pro-mutagens, blue-chitin extracts of human gallbladder bile (BCE) collected from the cholecystectomized patients with cholelithiasis were used in order to investigate the role of GUDCA on mutagen(s) actually existing in human bile. It was found that GUDCA did not show mutagenicity in this test system. Concerning the modification of mutagenic activities of pro-mutagens, GUDCA showed the different directions. GUDCA acted as co-mutagen, since it enhanced the mutagenic activities of 2AA and BaP. But, acted as anti-mutagen, since it suppressed the activities of Trp-P-2, IQ and MeIQ, all of which were classified as heterocyclic amines. GUDCA also suppressed the mutagen(s) in human bile. Because of the use of blue-chitin absorbed method for testing bile mutagenicity, the chemicals involved were considered to be heterocyclic amines and other polycyclic compounds. In these we suspect the bile mutagens are heterocyclic amines. Further examination should be directed towards the investigation into the mechanism of anti-mutagenic effects of GUDCA on mutagen(s) actually existing in human bile.