In vivo covalent binding of aflatoxin metabolites isolated from animal tissue to rat-liver DNA

Abstract

Ring-labelled [ 14C]aflatoxin B 1 (AFB 1), prepared by biosynthesis, or generally labelled [ 3H]AFB 1 was administered by oral gavage to young adult male rats. After 6 hr, the liver was removed and two fractions were isolated, namely macromolecules, which contained about 3% of the initial dose of AFB 1 radioactivity, and water-soluble, low-molecular aflatoxin conjugates containing about 0·2% of the administered radioactivity. These two fractions were administered orally to other rats in order to determine the potential of radioactive aflatoxin residues for covalent binding to DNA. Such binding can be used as an indicator for carcinogenic potency. Liver DNA was isolated 9–12 hr after administration of the aflatoxin derivatives and in no case was any radioactivity detected on the DNA. It can be deduced on the basis of the limit of detection of radioactivity on the DNA, that macromolecule-bound AFB 1 derivatives are at least 4000 times less active than AFB 1 with respect to covalent binding to rat-liver DNA, and that the water-soluble conjugates are at least 100 times less potent than AFB 1 itself. It is concluded that the carcinogenic risk for humans who consume liver or meat containing such aflatoxin residues is negligible when compared with the risk from intake of aflatoxins in other food items.