Biliary excretion, systemic availability and reactivity of metabolites following intraportal infusion of [3H]benzo[a]pyrene in the rat

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Abstract
Following the intraportal infusion of [ 3 H]benzo[a]-pyrene (BP) at two dose levels (5 and 0.125 μmol/kg) in the rat, metabolites were excreted via the bile and were released into the hepatic venous blood. At each dose level, a significant portion (approx. 15–18%) of biliary metabolites was directly extractable with ethyl acetate and a total of approx. 24–32% became extractable after incubation of bile with β-glucuronidase. More than 65% and 70% of the 3 H in blood and liver, respectively, was directly extractable with ethyl acetate. The h.p.l.c. profile of extracted metabolites was found to differ at the two dose levels studied. The binding of reactive metabolites to hepatic protein and DNA was measured at four dose levels of [ 3 H]BP. The possible availability of hepatic-derived metabolites to extrahepatic sites is discussed.