Interspecies differences in the hepatic metabolism of 2,3,7,8-tetrachlorodibenzo-p-dioxin: role in toxicity

These studies examined the hepatic metabolism of TCDD in suspensions of isolated hepatocytes from the guinea pig and hamster. 14C- TCDD was metabolized at a similar rate in hepatocytes from the three species. TCDD pretreatment 72 hours prior to hepatocyte isolation increased cytochrome P-448-mediated monooxygenase activities and increased the rate of TCDD metabolism in rat and hamster hepatocytes 5-6-fold over the control rate. However, pretreatment of guinea pigs with TCDD had not effect on the rate of 14C-TCDD metabolism in isolated hepatocytes from this species. The findings suggest that the inability of TCDD to induce its own rate of hepatic metabolism in the guinea pig may contribute to the persistence of TCDD and unique sensitivity of this species to the acute toxicity of TCDD