Effect of alpha-tocopherol on hepatocarcinogenesis in transforming growth factor-alpha (TGF-alpha) transgenic mice treated with diethylnitrosamine

To examine the potentially chemopreventive effects of alpha -tocopherol on hepatocarcinogenesis, we fed the transgenic mice line MT42, which overexpre sses transforming growth factor-alpha (TGF-alpha) and which has been establ ished as having a high incidence of liver tumor, with different concentrati ons of alpha -tocopherol and examined the hepatic tumorigenesis of these mi ce. At 3 weeks of age, MT42 male mice received a single intraperitoneal inj ection of diethylnitrosaimine (DEN), 5 mg/kg body weight, to initiate the f ormation of liver tumors. The mice were divided into three groups: group A, control diet (20 mg/kg of alpha -tocopherylacetate): group B, deficient di et (less than 1 mg/kg); group C, supplemented diet (500 mg/kg). Neoplastic change was determined at 40 weeks of age. The incidence of adenomas (p < 0. 05), the maximum tumor size (p < 0.01), the mean relative liver weight (p < 0.01), and the proliferating cell nuclear antigen (PCNA) labeling indices of the non-tumor sites (p < 0.01) of group B were significantly higher than . those of group C. No toxic effects of alpha -tocopherol were found. Alpha -tocopherol-deficient diet accelerated the hepatocarcinogenesis of TGF-alph a transgenic mice treated with DEN. At best, these data demonstrate that al pha -tocopherol-deficiency is not beneficial for prevention of hepatocarcin ogenesis in this model. Alpha-tocopherol may be useful for the chemoprevent ion for liver cancer.