Glauert H P, Beaty M M, Clark T D, Greenwell W S, Tatum V, Chen L C, Borges T, Clark T L, Srinivasan S R, Chow C K
Department of Nutrition and Food Science, Veterans Administration Hospital, Lexington, KY.
J Cancer Res Clin Oncol. 1990;116(4):351-6. doi: 10.1007/BF01612917.
The purpose of this study was to determine the effect of the dietary antioxidant vitamin E on hepatocarcinogenesis by peroxisome proliferators which, it is hypothesized, induce tumors by increased production of hydrogen peroxide or other oxygen radicals. Rats were fed diets containing the peroxisome proliferator ciprofibrate and one of three concentrations (10, 50, or 500 ppm) of alpha-tocopheryl acetate for 6 months or 21 months. The incidence of hepatic tumors and the number and volume of gamma-glutamyl-transpeptidase-positive, ATPase-negative, glucose-6-phosphatase-negative, and glucose-6-phosphatase-positive foci were quantified. No tumors or altered hepatic foci were seen at 6 months, but at 21 months the incidence of hepatic tumors and the number and volume of altered hepatic foci were increased in rats fed higher levels of vitamin E. Indices of oxidative damage--concentrations of malonaldehyde, conjugated dienes, and lipid-soluble fluorescence products--were not affected or were lower in rats fed higher amounts of vitamin E; the enhancing effect of vitamin E on the development of altered hepatic foci and hepatic tumors, therefore, was not related to the induction of cellular oxidative damage. Hepatic peroxisomal fatty acid beta-oxidation and vitamin C concentrations were not affected by vitamin E, whereas the glutathione concentration was decreased in rats fed higher amounts of vitamin E. This study shows that increasing the vitamin E content of the diet enhances ciprofibrate-induced hepatocarcinogenesis, but the mechanism of this effect is unclear.
本研究的目的是确定膳食抗氧化剂维生素E对过氧化物酶体增殖剂诱导肝癌发生的影响。据推测，过氧化物酶体增殖剂通过增加过氧化氢或其他氧自由基的产生来诱发肿瘤。给大鼠喂食含有过氧化物酶体增殖剂环丙贝特以及三种浓度（10、50或500 ppm）之一的α-生育酚醋酸酯的饲料，持续6个月或21个月。对肝肿瘤的发生率以及γ-谷氨酰转肽酶阳性、ATP酶阴性、葡萄糖-6-磷酸酶阴性和葡萄糖-6-磷酸酶阳性病灶的数量和体积进行了量化。在6个月时未观察到肿瘤或肝脏病灶改变，但在21个月时，喂食较高水平维生素E的大鼠肝肿瘤发生率以及肝脏病灶改变的数量和体积均增加。氧化损伤指标——丙二醛、共轭二烯和脂溶性荧光产物的浓度——在喂食较高量维生素E的大鼠中未受影响或较低；因此，维生素E对肝脏病灶改变和肝肿瘤发生发展的促进作用与细胞氧化损伤的诱导无关。肝过氧化物酶体脂肪酸β-氧化和维生素C浓度不受维生素E影响，而喂食较高量维生素E的大鼠谷胱甘肽浓度降低。本研究表明，增加饮食中维生素E的含量会增强环丙贝特诱导的肝癌发生，但这种作用的机制尚不清楚。
