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.
D000818:Animals; D001580:Benzopyrenes / Q000378:metabolism / Q000633:toxicity*; D001646:Bile / Q000378:metabolism*; D001711:Biotransformation; D005260:Female; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000235:genetics
D001580:Benzopyrenes; D009153:Mutagens; C017409:6-(hydroxymethyl)benzo(a)pyrene