Lack of Effect of Dietary α-Tocopherol on Chemically Induced Hepatocarcinogenesis in Rats

Abstract

We investigated the effects of α-tocopherol on diethylnitrosamine (DEN) initiation-phenobarbital (PB) promotion of hepatic foci in female Sprague-Dawley rats. Groups of eight rats were initiated with DEN (15 mg/kg) at 24 hours of age. After weaning, they received diets containing 500 ppm PB and various concentrations of α-tocopherol, deficient (0 ppm), adequate (100 ppm), and supplemented (5,000 ppm), for 24 weeks. Rats fed α-tocopherol-supplemented diets had significantly greater hepatic α-tocopherol levels than those fed α-tocopherol-deficient or -adequate diets (p < 0.05). Liver lipid peroxidation (measured as thiobarbituric acid-reactive substances) was significantly greater in rats fed α-tocopherol-deficient diets than in those fed α-tocopherol-adequate or -supplemented diets (p < 0.05). The dietary α-tocopherol level had no significant effect on the ratios of reduced glutathione (GSH) to oxidized GSH or reduced GSH to total GSH in the liver or on the plasma prostaglandin E2 concentration or on the activities of hepatic cytosolic and particulate protein kinase C. Rats fed α-tocopherol-adequate or -supplemented diets had significantly greater hepatic glutathione S-transferase, GSH reductase, and GSH peroxidase activities than those fed α-tocopherol-deficient diets (p < 0.05). The dietary α-tocopherol level did not significantly affect the formation of hepatic γ-glutamyl transpeptidase- and placental glutathione S-transferase-positive foci. These results suggest that α-tocopherol does not influence hepatic foci formation and that reactive oxygen species may not be the underlying mechanism of hepatic foci formation in this DEN initiation-PB promotion model of hepatocarcinogenesis.