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饮食中无机硒过量对F344大鼠结肠癌发生起始阶段和起始后阶段的影响。

Effect of dietary excess of inorganic selenium during initiation and postinitiation phases of colon carcinogenesis in F344 rats.

作者信息

Reddy B S, Sugie S, Maruyama H, Marra P

机构信息

Division of Nutrition, Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, New York 10595.

出版信息

Cancer Res. 1988 Apr 1;48(7):1777-80.

PMID:3349457
Abstract

The effect of supplemental inorganic selenium given during the initiation or postinitiation phase of colon carcinogenesis induced by azoxymethane [(AOM)CAS:25843-45-2] was studied in male F344 rats. Weanling animals were raised on AIN-76A semipurified (control) diet. Starting at 4 wk of age, groups of animals intended for initiation study were fed the semipurified diets containing 0.5 and 2.5 ppm selenium in the form of sodium selenite, and those intended for postinitiation study were continued on the control diet. At 7 wk of age, all animals except the vehicle-treated controls were injected s.c. with AOM (15 mg/kg body weight, once weekly for 2 wk). One wk following AOM treatment, animals in the initiation study receiving the supplemental selenium were transferred to the control diet whereas those in the postinitiation study receiving the control diet were transferred to the diets containing 0.5 and 2.5 ppm selenium. These animals were continued on this regimen until the termination of the experiment at 34 wk post-AOM injection. Tissue and blood glutathione peroxidase activity was measured in vehicle-treated animals fed the control and selenium-supplemented diets. The results indicate that body weights were comparable among the various dietary groups. Feeding of diets containing 0.5 and 2.5 ppm selenium during the initiation phase had no effect on colon tumor incidence, but the multiplicity of adenomas was slightly inhibited in animals fed the 2.5 ppm selenium diet. The incidence and multiplicity of colon adenocarcinomas and the multiplicity of colon adenomas were inhibited in animals fed the 2.5-ppm selenium diet during the postinitiation phase of carcinogenesis. The incidence of small intestinal tumors was higher in animals fed the 2.5-ppm selenium diet during the initiation phase than in animals fed the control diet and 0.5-ppm selenium diet. Selenium-dependent glutathione peroxidase activity was increased in kidneys and small and large intestinal mucosae of animals fed the 2.5-ppm selenium diet compared to those fed the 0.5-ppm selenium and control diets.

摘要

在雄性F344大鼠中,研究了在由氧化偶氮甲烷[(AOM),CAS:25843-45-2]诱导的结肠癌发生起始期或起始后期给予补充无机硒的效果。断奶动物用AIN-76A半纯化(对照)饮食饲养。从4周龄开始,用于起始研究的动物组喂食含有0.5和2.5 ppm亚硒酸钠形式硒的半纯化饮食,而用于起始后期研究的动物继续喂食对照饮食。在7周龄时,除溶剂处理的对照外,所有动物均皮下注射AOM(15 mg/kg体重,每周一次,共2周)。AOM处理后1周,起始研究中接受补充硒的动物转至对照饮食,而起始后期研究中接受对照饮食的动物转至含有0.5和2.5 ppm硒的饮食。这些动物继续该方案,直到在AOM注射后34周实验结束。在喂食对照和补充硒饮食的溶剂处理动物中测量组织和血液谷胱甘肽过氧化物酶活性。结果表明,各饮食组之间体重相当。在起始期喂食含有0.5和2.5 ppm硒的饮食对结肠癌发病率没有影响,但喂食2.5 ppm硒饮食的动物中腺瘤的多发性略有抑制。在致癌作用的起始后期,喂食2.5 ppm硒饮食的动物中结肠腺癌的发病率和多发性以及结肠腺瘤的多发性受到抑制。在起始期喂食2.5 ppm硒饮食的动物中小肠肿瘤的发病率高于喂食对照饮食和0.5 ppm硒饮食的动物。与喂食0.5 ppm硒和对照饮食的动物相比,喂食2.5 ppm硒饮食的动物的肾脏以及小肠和大肠粘膜中硒依赖性谷胱甘肽过氧化物酶活性增加。

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