Department of Pathology, University of Illinois at Chicago, 840 South Wood Street, Chicago, IL 60612, USA.
Cancer Prev Res (Phila). 2010 Mar;3(3):371-80. doi: 10.1158/1940-6207.CAPR-09-0152. Epub 2010 Feb 23.
Previous studies with selenium and/or vitamin E in prostate carcinogenesis animal models have been negative, but these models may not involve oxidative stress mechanisms. In this study, we examined the potential of selenomethionine and alpha-tocopherol to modulate prostate cancer development in the testosterone plus estradiol-treated NBL rat, a model that does involve sex hormone-induced oxidative stress mechanisms and prostatic inflammation. One week following the implantation with hormone-filled Silastic implants, rats were fed diets containing l-selenomethionine (1.5 or 3.0 mg/kg), DL-alpha-tocopherol acetate (2,000 or 4,000 mg/kg), or a natural ingredient control diet (NIH-07). The development of prostate carcinomas was not affected by dietary treatment with either agent. Food intake, body weight, and mortality were also not affected. The high dose of selenomethionine reduced the severity of epithelial dysplasia in the lateral prostate that was not associated with inflammation, and alpha-tocopherol reduced in a dose-related fashion the incidence of marked inflammation and marked epithelial dysplasia in the lateral prostate, regardless of whether these lesions were associated with inflammation. alpha-Tocopherol significantly increased the incidence of adenocarcinomas of the mammary glands at both dietary concentrations. Collectively, our findings suggest that selenomethionine and alpha-tocopherol supplementation does not prevent prostate cancer in rats fed diets with nutritionally adequate levels of selenium and vitamin E. Importantly, the results of the current animal studies and those reported previously were fully predictive of the outcome of the Selenium and Vitamin E Cancer Prevention Trial.
先前关于硒和/或维生素 E 在前列腺癌发生动物模型中的研究结果为阴性，但这些模型可能不涉及氧化应激机制。在这项研究中，我们研究了硒蛋氨酸和 α-生育酚是否具有调节经睾丸酮加雌二醇处理的 NBL 大鼠前列腺癌发展的潜力，该模型涉及性激素诱导的氧化应激机制和前列腺炎症。在植入充满激素的硅橡胶植入物后一周，大鼠喂食含 l-硒蛋氨酸（1.5 或 3.0mg/kg）、DL-α-生育酚乙酸酯（2000 或 4000mg/kg）或天然成分对照饮食（NIH-07）的饮食。两种药物的饮食处理均未影响前列腺癌的发展。食物摄入量、体重和死亡率也不受影响。高剂量的硒蛋氨酸降低了侧前列腺上皮异型增生的严重程度，且与炎症无关，而 α-生育酚以剂量相关的方式降低了侧前列腺中明显炎症和明显上皮异型增生的发生率，而不论这些病变是否与炎症相关。α-生育酚在两种饮食浓度下均显著增加了乳腺腺癌的发生率。总的来说，我们的研究结果表明，在喂食具有足够营养水平的硒和维生素 E 的饮食的大鼠中，补充硒蛋氨酸和 α-生育酚并不能预防前列腺癌。重要的是，目前动物研究的结果和以前报告的结果完全预测了硒和维生素 E 癌症预防试验的结果。
