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Effects of Dietary Fat on Hepatic Mixed-Function Oxidases and Hepatocellular Carcinoma Induced by Aflatoxin B₁ in Rats¹

Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139

Some groups of male Sprague-Dawley rats were fed a diet containing either 28% beef fat and 2% corn oil or 30% corn oil (high fat), and others were fed either 13% beef fat and 2% corn oil or 15% corn oil (moderate fat), for varying periods of time, with or without exposure to aflatoxin B₁ (AFB₁). Assays for hepatic microsomal oxidases [p-nitroanisole demethylase and benzo(a)pyrene hydroxylase] were performed on liver samples to determine the activity associated with the two types of fat at different dietary concentrations. Beef fat increased liver fat concentrations and resulted in a higher mortality rate from a dose of AFB₁ at which 50% of animals died, compared to corn oil-fed groups. In an additional study, the resting levels of microsomal enzyme activity increased sequentially in all groups over a 3-week period after animals were placed on the respective diets. Corn oil diets permitted the greatest increase (induction) in activity of both enzymes at weekly intervals for 3 weeks. In another experiment, in which rats from all dietary groups were exposed to AFB₁, corn oil permitted a significantly higher induction of enzyme activity by AFB₁. In a 14-month study of rats fed the high corn oil diet, those exposed to the diet during and after AFB₁ treatment developed significantly more liver tumors than those consuming the diet only after administration of a carcinogenic dose of AFB₁. In animals fed beef fat, tumor incidence was depressed compared to those fed corn oil, but no differences were observed between groups fed beef fat throughout exposure to AFB₁ and after ward and those fed beef fat only after AFB₁ exposure. These observations suggest that corn oil may act as a promoter through microsomal enzyme induction and AFB₁ activation.

¹ This work supported in part by grants from G. D. Searle & Co., Chicago, Ill., and Hoffmann-LaRoche Inc., Nutley, N. J., and by Grant PO1-ES00597 from the National Institute of Environmental Health Sciences, Department of Health, Education, and Welfare.

² To whom requests for reprints should be addressed, at Room E18-613, Massachusetts Institute of Technology, Cambridge, Mass. 02139.

Received 1/ 8/79. Accepted 7/ 5/79.

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