Modification of mutagenic activities of pro-mutagens by glyco-ursodeoxycholic acid in the Ames assay

Mutagenicity, co-mutagenicity and anti-mutagenicity of glyco-ursodeoxycholi c acid (G-UDCA) were examined by the Ames assay using Salmonella typhimuriu m strain TA98 with S9. As pro-mutagens, 2-aminoanthracene (2AA), Benzo[a]py rene (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 promutagens, blue-chi tin extracts of human gallbladder bile (BCE) collected from the cholecystec tomized patients with cholelithiasis were used in order to investigate the role of GUDCA on mutagen(s) actually existing in human bile. It was found t hat GUDCA did not show mutagenicity in this test system. Concerning the mod ification of mutagenic activities of pro-mutagens, GUDCA showed the differe nt directions. GUDCA acted as co-mutagen, since it enhanced the mutagenic a ctivities of 2AA and BaP. But, acted as anti-mutagen since it suppressed th e activities of Trp-P-a, IQ and MeIQ, all of which were classified as heter ocyclic amines. GUDCA also suppressed the mutagen(s) in human bile. Because of the use of blue-chitin absorbed method for testing bile mutagenicity, t he chemicals involved were considered to be heterocyclic amines and other p olycyclic compounds. In these we suspect the bile mutagens are heterocyclic amines. Further examination should be directed towards the investigation i nto the mechanism of anti-mutagenic effects of GUDCA on mutagen(s) actually existing in human bile.