Mutagenicity and in vivo disposition of biliary metabolites of benzo(a)pyrene.
Rabbits and rats administered [3H]benzo(a)pyrene (BP; 40 mumol/kg, i.v.) excreted, via the bile, metabolites which increased reverse gene mutation frequency in Salmonella typhimurium TA98 when incubated with beta-glucuronidase. Glucuronic acid conjugates of BP 4,5-diol, BP 1,6-, 3,6- and 6,12-quinones were detected in rat bile with low levels of 3- and 9-OH BP and BP 7,8- and 9,10-diols. In rabbits BP 9,10-diol was the major aglycone along with smaller amounts of BP 1,6- and 3,6-quinones, BP 4,5- and 7,8-diols and 3- and 9-OH BP. Qualitatively similar metabolic profiles were found when animals were given 3 mumol/kg [3H]BP. When 3H-labelled biliary metabolites, which contained the mutagenic component, were administered intraduodenally to rats, radioactivity reached the systemic circulation but DNA adducts were not detectable (less than 0.03 pmol/mg DNA) in tissues (intestinal wall, liver and lung) exposed to the reabsorbed metabolites.
D000818:Animals; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism / Q000633:toxicity*; D001646:Bile / Q000378:metabolism*; D001711:Biotransformation; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects; D014316:Tritium
D001580:Benzopyrenes; D009153:Mutagens; D014316:Tritium; D001564:Benzo(a)pyrene; D004247:DNA