Effects of chronic exposure to aflatoxin B1and aflatoxin M1on thein vivocovalent binding of aflatoxin B1to hepatic macromolecules

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Abstract
Induction of resistance to aflatoxin B1 (AFB1) binding to cellular macromolecules in the rat by chronic exposure to AFB1 and aflatoxin M1 (AFM1) was investigated. The binding of [14C]AFB1 to liver macromolecules was measured in F-344 rats fed 0.5 or 50 ppb AFM1 or 50 ppb AFB1 for 41 wk. The animals received an intragastric dose of [14C]AFB1 at 5 .mu.g/kg and were sacrificed 6 h later. Hepatic DNA, RNA and protein were isolated by chloroform-phenol extraction and hydroxylapatite chromatography. In animals preexposed to 50 ppb AFB1, labeled AFB1 binding to DNA, RNA and protein was decreased by 72, 74 and 61%, respectively. Preexposure to AFM1 resulted in a small reduction in binding to nucleic acids. Glutathione transferase activity was increased by 133% in animals fed 50 ppb AFB1, by 48% in those preexposed to 50 ppb AFM1 and remained at control values in rats fed 0.5 ppb AFM1. The induction of detoxification enzymes following chronic exposure to aflatoxin might have contributed to the reduction in covalent binding of AFB1 to macromolecules.