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.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D004247:DNA / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008298:Maleates / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D012313:RNA / Q000378:metabolism*; D051381:Rats
D000348:Aflatoxins; D008298:Maleates; D011506:Proteins; D012313:RNA; D004247:DNA; D016604:Aflatoxin B1; C014476:diethyl maleate; D005978:Glutathione