Benzo (a) Pyrene Metabolism and Enterohepatic Circulation in the Rat
The polycyclic aromatic hydrocarbon benzo(a)pyrene* is metabolically activated by monooxygenase and epoxide hydrolase (EC. 184.108.40.206) to reactive intermediates, which are mutagenic, cytotoxic and carcinogenic (1–3). The metabolic profile obtained by incubation of BP with various mammalian systems in vitro has been investigated (4). However, the fate of BP in vivo has received relatively little attention. Metabolites of BP are excreted via the bile in the rat (5) and rabbit (6) and BP metabolites in rat bile have recently been shown to be mutagenic to tester strains of Salmonella typhimurium (7). Rat and human intestinal microflora are capable of hydrolyzing conjugates of BP metabolites (8) to release relatively non-polar aglycones.
KeywordsEpoxide Hydrolase ENTEROHEPATIC Circulation Bile Sample Polar Metabolite Glucuronic Acid Conjugate
Unable to display preview. Download preview PDF.
- 3.International Agency for Research on Cancer. IARC monographs on the evaluation of carcinogenic risk of chemicals to man. Vol. 3, Lyon, France, (1973).Google Scholar
- 4.P.W. Jones and R.I. Freudenthal, Polynuclear aromatic hydrocarbons: 2nd Int. Symp. on analysis, chemistry and biology, Carcinogenesis, A Comprehensive Survey, Vol. 3 (1978).Google Scholar
- 5.H.L. Falk, P. Kotin, S.S. Lee and A.J. Nathan, Intermediary metabolism of benzo(a)pyrene in the rat. J. Natl. Cancer Inst. 28: 699 (1962).Google Scholar
- 6.J.K. Chipman, P.C. Hirom, G.S. Frost and P. Millburn, Species variation in the metabolism and excretion of benzo(a)pyrene. Proc. British Assoc. Cancer Res. 21st A.G.M. Southampton (1980).Google Scholar
- 8.A.G. Renwick and B.S. Drasar, Environmental Carcinogens and large bowel cancer, Nature (Lond.) 263: 234 (1976).Google Scholar
- 9.J.K. Chipman and N.C. Cropper, A technique for chronic intermittent bile collection from the rat, Res. Vet. Sci. 22: 366 (1977).Google Scholar
- 10.J.L. Plummer, B.R. Smith, L.M. Ball and J.R. Bend, Metabolism and biliary excretion of benzo(a)pyrene 4,5-oxide in the rat, Drug Metab. Disp. 8: 68 (1980).Google Scholar