Nutrition and Cancer Vitamin E Inhibits Hepatic NF- B Activation in Rats Administered the Hepatic Tumor Promoter, Phenobarbital

Phenobarbital (PB) is an efficacious hepatic tumor promoter. Although the promoting activity of PB is likely related to altered cell proliferation or apoptosis, the induction of an oxidative stress environment may also be important. PB has been shown to activate the transcription factor nuclear factorB (NFB). In this study, we hypothesized that PB-induced NFB activation can be decreased by dietary vitamin E in rats. Male SpragueDawley rats (n 39) were fed a purified diet with varying levels of dietary vitamin E (10, 50 or 250 mg/kg of dl-tocopherol acetate) for 28 d, at which time 8 rats per level of dietary vitamin E were fed the same diet with 500 mg/kg PB for 10 d. In the rats fed the low vitamin E diet, PB increased NFB DNA binding, but it did not affect NFB activation in rats fed higher levels of vitamin E (50 and 250 mg/kg). Vitamin E may decrease the oxidative stress created by PB by also enhancing other antioxidants; therefore, we also measured hepatic glutathione S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase and NAD(P)H: quinone reductase (DT-diaphorase) activities and glutathione and ascorbic acid concentrations. Increased dietary -tocopherol did not affect the antioxidants and antioxidant enzymes altered by PB treatment. Thus, the effect of -tocopherol acetate on NFB activation does not appear to be mediated by alterations in the antioxidant system. These results demonstrate that the activation of NFB, a transcription factor that affects cell proliferation– and apoptosis-related gene expression, can be inhibited by dietary vitamin E. J. Nutr. 132: 3178–3185, 2002.