Mutagenic activity of biliary metabolites of 6-hydroxymethylbenzo[a]pyrene.

The biliary excretion of the carcinogen 6-hydroxy-methylbenzo[a]pyrene was investigated in rats after i.p. administration. Mutagenicity of the parent compound and its biliary metabolites was tested in Ames Salmonella/microsome mutagenicity assay. Approximately 40% of the dose administered (0.25-0.5 mg/kg) to the rats was excreted in the bile within 6 h. 6-Hydroxymethylbenzo[a]pyrene was excreted primarily as water-soluble metabolites, including glucuronide and sulfate conjugates. Negligible quantities of unchanged 6-hydroxymethylbenzo[a]pyrene were excreted in the bile. In the presence of Aroclor-induced S9, 6-hydroxymethylbenzo[a]pyrene was a potent mutagen. The mutagenicity of bile from rats treated with 6-hydroxymethylbenzo[a]pyrene was variable in the absence of an activation system. However, the same bile samples were mutagenic in the presence of beta-glucuronidase and/or S9. These results indicate that biliary metabolites of 6-hydroxymethylbenzo[a]pyrene can be metabolically activated to mutagenic species.