Glauert H P, Beaty M M, Clark T D, Greenwell W S, Chow C K
Department of Nutrition and Food Science, Veterans Administration Hospital, University of Kentucky, Lexington 40506.
Nutr Cancer. 1990;14(3-4):261-71. doi: 10.1080/01635589009514102.
The purpose of this study was to determine if the dietary antioxidant selenium could inhibit hepatocarcinogenesis induced by peroxisome proliferators, which are hypothesized to induce tumors by increased production of hydrogen peroxide or other reactive oxygen species. Rats were fed diets containing the peroxisome proliferator ciprofibrate and one of three concentrations (0.04, 0.2, or 1.0 ppm) of selenium for 6 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 at 21 months were lower in rats fed higher levels of selenium (no foci or tumors were seen at 6 mo). Indices of oxidative damage in the liver (thiobarbituric acid reactants, conjugated dienes, and lipid-soluble fluorescence products), however, were not decreased in rats fed the high-selenium diet. Therefore, selenium was protective against ciprofibrate-induced hepatocarcinogenesis, but not by reducing the degree of oxidative damage. The liver selenium and glutathione concentrations, and liver selenium-dependent glutathione peroxidase activity, increased as dietary selenium increased. Therefore, inhibition of carcinogenesis by selenium was correlated with increased levels of glutathione and glutathione peroxidase, but these did not inhibit the indices of oxidative damage. Peroxisomal beta-oxidation also increased with the dietary selenium content; it therefore does not appear to be a factor in the inhibition of hepatocarcinogenesis in rats fed higher levels of selenium.
本研究的目的是确定膳食抗氧化剂硒是否能抑制过氧化物酶体增殖剂诱导的肝癌发生，据推测，过氧化物酶体增殖剂通过增加过氧化氢或其他活性氧的产生来诱导肿瘤。给大鼠喂食含有过氧化物酶体增殖剂环丙贝特和三种浓度（0.04、0.2或1.0 ppm）硒之一的饲料，持续6个月或21个月。在21个月时，喂食较高水平硒的大鼠肝肿瘤发生率以及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-磷酸酶阳性灶的数量和体积较低（在6个月时未观察到灶或肿瘤）。然而，喂食高硒饲料的大鼠肝脏中的氧化损伤指标（硫代巴比妥酸反应物、共轭二烯和脂溶性荧光产物）并未降低。因此，硒对环丙贝特诱导的肝癌发生具有保护作用，但不是通过降低氧化损伤程度来实现的。肝脏硒和谷胱甘肽浓度以及肝脏硒依赖性谷胱甘肽过氧化物酶活性随着膳食硒的增加而增加。因此，硒对致癌作用的抑制与谷胱甘肽和谷胱甘肽过氧化物酶水平的增加相关，但这些并未抑制氧化损伤指标。过氧化物酶体β-氧化也随着膳食硒含量的增加而增加；因此，它似乎不是喂食较高水平硒的大鼠肝癌发生抑制的一个因素。
