METABOLISM OF AFLATOXIN-B1 IN CULTURED MOUSE HEPATOCYTES - COMPARISON WITH RAT AND EFFECTS OF CYCLOHEXENE OXIDE AND DIETHYL MALEATE

The metabolism of aflatoxin B1 was studied in cultured hepatocytes from adult male mice. After a 10-hr incubation, 89% of the dose of [14C]aflatoxin B1 was converted to aqueous metabolites, while 0.77% was covalently bound to cellular macromolecules. In contrast, it has been previously shown that hepatocytes cultured from the rat and incubated with aflatoxin B1 form 57.2% aqueous metabolites and covalently bind 12.2% to cellular macromolecules. The nearly 16-fold greater covalent binding in rat hepatocytes correlates with the greater susceptibility of the rat to the hepatocarcinogenic effect of aflatoxin B1. Diethyl maleate and cyclohexene oxide each was shown to significantly increase the amount of covalent binding in hepatocytes from both species. At 10-3 m, diethyl maleate and cyclohexene oxide, respectively, produced 805 and 61% increase in covalent binding in mouse hepatocytes, suggesting that both diol formation and glutathione conjugation are important detoxification pathways for aflatoxin B1. Both pathways are apparently more active in mouse hepatocytes than in rat hepatocytes. © 1979.