Effect of monooxygenase inducers and inhibitors on the hepatic metabolism of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rat and hamster, Drug Metab. Dispos

The rat and hamster exhibit about a 100-fold difference in sensitlvfty to the acute toxicfty of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), with the hamster representing the most resistant species examined to date. The present study compared the induction and inhibition of hepatic TCDD metabolism in these species using suspensions of isolated hepatocytes. Purified C-TCDD or H-TCDD (2.2 giM) was incubated for2-6 hr with hepatocytes isolated from untreated, TCDD-pretreated (5 gig/kg, ip), 3-methylchoianthrene-pretreated (3-MC, 50 mg/kg, ip, x 3 days), isosafrole-pretreated (ISO, 150 mg/kg, ip, x 3 days), or phenobarbital-pretreated (PB, 80 mg/kg, ip, x 3 days) rats and hamsters. Untreated rat and hamster hepatocytes metabolized TCDD at a similar rate (0.20 and 0.18 pmol/hr/mg, respectively). In both species, TCDD and 3-MC pretreatments elevated the rate of TODD metabolism by 5-6-fold, while PB pretreatment had no effect Isosafrole modestly increased (1.8-2.5-fold) TCDD metabolism i