INDUCTION OF CYTOCHROME P4501A1 AND P4504A1 ACTIVITIES AND PEROXISOMAL PROLIFERATION BY FUMONISIN B-1

The effects of repeated exposure to fumonisin B-1 (FB1) on hepatic and renal mixed function oxidase activities and peroxisomal proliferation has been examined in rats following intraperitoneal administration at three dose levels (0.125, 0.25, and 2.5 mg/kg) once a day for 6 days. At the two highest doses, FB1 increased the renal and hepatic N-demet hylation of erythromycin (CYP3A1) and the hepatic O-deethylation of et hoxyresorufin (CYP1A1). FB1, at the highest dose of 2.5 mg/kg, also in creased the renal O-deethylation of ethoxyresorufin. The liver, but no t the kidney, was also susceptible to FB1-dependent induction of the 1 2- and 11-hydroxylation of lauric acid, suggesting induction of the CY P4A subfamily. Immunoblot studies employing solubilized microsomes fro m FB1-treated rats revealed that FB1, at the two highest doses, increa sed the apoprotein levels of CYP1A1 and CYP4A1. The same treatment wit h FB1 increased the beta-oxidation of palmitoyl-coenzyme A (CoA) in li ver homogenates, and immunoblot analysis showed an increase in the apo protein levels of the trans-2-enoyl-CoA hydratase trifunctional protei n. The possible implications of these findings to the hepatocarcinogen icity of this mycotoxin are discussed. (C) 1996 Academic Press, Inc.