Production and release of benzo(a)pyrene phenols from the perfused rat liver

The metabolism of benzo(a)pyrene (20 ..mu..M) to phenolic metabolites was examined in the non-recirculating perfused rat liver. The majority of free and conjugated phenols remained in the liver. Glucuronide conjugates were the primary metabolites released into bile and perfusate. Glucuronide and sulfate conjugates were concentrated approximately 3-fold in bile, suggesting transport by an active process. Release of glucuronide conjugates and free phenols into the perfusate was facilitated by albumin. Inhibition of glucuronidation by pretreatment with galactosamine (600 mg/kg, i.p.) decreased the intracellular concentration and release of glucuronide conjugates by >90%, without affecting the formation or release of sulfate conjugates or free phenols. Perfusion with sulfate-free buffer decreased the intracellular concentration of sulfate conjugates by 60%, but did not affect the rate of sulfate conjugate release from the liver. Intracellular concentrations of glucuronides and unconjugated phenols were unaffected by inhibition of sulfation; however, release of glucuronides into perfusate was enhanced approximately 2.5-fold. These data suggest that glucuronidation can regulate rates of production and release of benzo(a)pyrene phenols from liver.