Effect of 3-Methylcholanthrene Pretreatment on Aflatoxin B₁ Metabolism in Hamster Liver

Abstract

The effects of 3-methylcholanthrene (MC) pretreatment of hamsters on the hepatic metabolism of aflatoxin B₁ (AFB₁) have been investigated in studies with subcellular, isolated hepatocytes and in vivo. Pretreatment of hamsters with MC (2.5 mg/100 g body wt.) 24 hr. before sacrifice not only increased microsomal cytochrome P-450 content by 70% but also increased the specific activity of cytochrome P-450 dependent metabolic activation of AFB₁ as judged by AFB₁-DNA binding by 65%. Even in isolated hepatocytes, AFB₁-DNA binding was elevated by 65% in MC-treated hepatocytes. The ratios of AFB₁-glutathione (AFB₁-SG) to AFB₁-DNA were about the same in both hepatocyte system. Hepatic AFB₁-DNA binding was also increased by 85% in intact animals after MC treatment. It appears that the increased hepatic AFB₁-DNA binding after MC treatment of hamsters is a result of higher specific activity and higher levels of cytochrome P-450 species involved in the activation of AFB₁.