Transforming Growth Factor alpha in Mice

Effect of a-Tocopherol on Hepatocarcinogenesis in Transforming Growth Factor-a (TGF-a) Transgenic Mice Treated with Diethylnitrosamine

Satoru Kakizaki, Hitoshi Takagi1, Toshio Fukusato2, Mitsuo Toyoda, Norio Horiguchi, Ken Sato, Hisashi Takayama, Takeaki Nagamine and Masatomo Mori1

1 The First Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Gunma 371-8511 Japan 2 Department of Pathology, Gunma University Hospital, Maebashi, Gunma 371-8511 Japan

Summary To examine the potentially chemopreventive effects of a-tocopherol on hepatocarcinogenesis, we fed the transgenic mice line MT42, which overexpresses transforming growth factor-a (TGF-a) and which has been established as having a high incidence of liver tumor, with different concentrations of a-tocopherol and examined the hepatic tumorigenesis of these mice.

At 3 weeks of age, MT42 male mice received a single intraperitoneal injection of diethylnitrosamine (DEN), 5 mg/kg body weight, to initiate the formation of liver tumors. The mice were divided into three groups: group A, control diet (20 mg/kg of a-tocopherylacetate); group B, deficient diet (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 a-tocopherol were found.

Alpha-tocopherol-deficient diet accelerated the hepatocarcinogenesis of TGF-a transgenic mice treated with DEN. At best, these data demonstrate that a-tocopherol-deficiency is not beneficial for prevention of hepatocarcinogenesis in this model.

Alpha-tocopherol may be useful for the chemoprevention for liver cancer.

International Journal for Vitamin and Nutrition Research, Band 71, 2001, Heft 5, © Verlag Hans Huber AG, Bern

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