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 overexpresses transforming growth factor-alpha (TGF-alpha) and which has been established as having a high incidence of liver tumor, with different concentrations of alpha-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 alpha-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 alpha-tocopherol were found. Alpha-tocopherol-deficient diet accelerated the hepatocarcinogenesis of TGF-alpha transgenic mice treated with DEN. At best, these data demonstrate that alpha-tocopherol-deficiency is not beneficial for prevention of hepatocarcinogenesis in this model. Alpha-tocopherol may be useful for the chemoprevention for liver cancer.
Kakizaki
S
S
First Department of Internal Medicine, Gunma University School of Medecine, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511, Japan. kakizaki@niehs.nih.gov
Takagi
H
H
Fukusato
T
T
Toyoda
M
M
Horiguchi
N
N
Sato
K
K
Takayama
H
H
Nagamine
T
T
Mori
M
M
D000477:Alkylating Agents / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D018890:Chemoprevention; D004052:Diethylnitrosamine / Q000633:toxicity*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016211:Transforming Growth Factor alpha / Q000032:analysis* / Q000187:drug effects*; D024502:alpha-Tocopherol / Q000627:therapeutic use*
D000477:Alkylating Agents; D000975:Antioxidants; D016211:Transforming Growth Factor alpha; D004052:Diethylnitrosamine; D024502:alpha-Tocopherol