Lack of effect of dietary alpha-trocopherol on chemically induced hepatocarcinogenesis in rats

We investigated the effects of alpha-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 alpha-tocopherol, deficient (0 ppm), adequate (10 0 ppm), and supplemented (5,000 ppm), for 24 weeks. Rats fed alpha-tocopher ol-supplemented diets had significantly greater hepatic alpha-tocopherol le vels than those fed alpha-tocopherol-deficient or -adequate diets (p < 0.05 ). Liver lipid peroxidation (measured as thiobarbituric acid-reactive subst ances) was significantly greater in rats fed alpha-tocopherol-deficient die ts than in those fed alpha-tocopherol-adequate or -supplemented diets (p < 0.05). The dietary alpha-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 E-2 concentration or on th e activities of hepatic cytosolic and particulate protein kinase C. Rats fe d alpha-tocopherol-adequate or -supplemented diets had significantly greate r hepatic glutathione S-transferase, GSH reductase, and GSH peroxidase acti vities than those fed alpha-tocopherol-deficient diets (p < 0.05). The diet ary alpha-tocopherol level did not significantly affect the formation of he patic gamma-glutamyl transpeptidase- and placental glutathione S-transferas e-positive foci. These results suggest that alpha-tocopherol does not influ ence hepatic foci formation and that reactive oxygen species may not be the underlying mechanism of hepatic foci formation in this DEN initiation-PB p romotion model of hepatocarcinogenesis.