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Linear Dose-Response Curve for the Hepatic Macromolecular Binding of Aflatoxin B₁ in Rats at Very Low Exposures¹

Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853

The possibility of a low dose threshold for rat liver macromolecular binding of aflatoxin B₁ was investigated. Doses in ng/kg of radiolabeled aflatoxin B₁ produced measurable covalent binding of aflatoxin to DNA, RNA, and protein, and the extent of this binding increased linearly over a dose range of 10 to 1000 ng/kg. Macromolecular adduct formation was observed at the lowest dose used (10 ng/kg) which is within the human exposure range. Although diethyl maleate caused a reduction in hepatic glutathione from 5 to 2.3 µmol/g of liver and a slight increase in macromolecular adduct levels, the dose-response curve for macromolecular adduct formation remained linear in both diethyl maleate-pretreated and control groups. These results indicate that macromolecular binding of aflatoxin B₁ is essentially a linear function of dose at low exposures and that hepatic glutathione offers little if any protection against this binding.

¹ This project was partially supported by American Cancer Grant PT 104 and by National Cancer Institute Grant PO1 CA 26755.

² To whom requests for reprints should be addressed.

Received 9/16/81. Accepted 5/12/82.

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