Linear dose-response curve for the hepatic macromolecular binding of aflatoxin B1 in rats at very low exposures

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 mumol/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.