Effects of chronic exposure to aflatoxin B₁ and aflatoxin M₁ on the in vivo covalent binding of aflatoxin B₁ to hepatic macromolecules

Abstract

Induction of resistance to aflatoxin B ₁ (AFB ₁ ) binding to cellular macromolecules in the rat by chronic exposure to AFB ₁ and aflatoxin M ₁ (AFM ₁ ) was investigated. The binding of [ ¹⁴ C]AFB ₁ to liver macromolecules was measured in F‐344 rats fed 0.5 ppb or 50 ppb AFM ₁ or 50 ppb AFB ₁ for 41 wk. The animals then received an intragastric dose of [ ¹⁴ C]AFB ₁ at 5 μg/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 AFB ₁ , labeled AFB ₁ binding to DNA, RNA, and protein was decreased by 72%, 74%, and 61%, respectively. Preexposure to AFM ₁ resulted in a small reduction in binding to nucleic acids. Glutathione trans‐ferase activity was increased by 133% in animals fed 50 ppb AFB ₁ , by 48% in those preexposed to 50 ppb AFM ₁ , and remained at control values in rats fed 0.5 ppb AFM ₁ . These results suggest that the induction of detoxification enzymes following chronic exposure to aflatoxin might contribute to the reduction in covalent binding of AFB ₁ to macromolecules.