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首页> 外文期刊>Dose-response >Defining the Optimal Selenium Dose for Prostate Cancer Risk Reduction: Insights from the U-Shaped Relationship between Selenium Status, DNA Damage, and Apoptosis
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Defining the Optimal Selenium Dose for Prostate Cancer Risk Reduction: Insights from the U-Shaped Relationship between Selenium Status, DNA Damage, and Apoptosis

机译：确定降低前列腺癌风险的最佳硒剂量：从硒状态，DNA损伤和凋亡之间呈U型关系的见解

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Our work in dogs has revealed a U-shaped dose response between selenium status and prostatic DNA damage that remarkably parallels the relationship between dietary selenium and prostate cancer risk in men, suggesting that more selenium is not necessarily better. Herein, we extend this canine work to show that the selenium dose that minimizes prostatic DNA damage also maximizes apoptosis—a cancer-suppressing death switch used by prostatic epithelial cells. These provocative findings suggest a new line of thinking about how selenium can reduce cancer risk. Mid-range selenium status (.67–.92 ppm in toenails) favors a process we call “homeostatic housecleaning”—an upregulated apoptosis that preferentially purges damaged prostatic cells. Also, the U-shaped relationship provides valuable insight into stratifying individuals as selenium-responsive or selenium-refractory, based upon the likelihood of reducing their cancer risk by additional selenium. By studying elderly dogs, the only non-human animal model of spontaneous prostate cancer, we have established a robust experimental approach bridging the gap between laboratory and human studies that can help to define the optimal doses of cancer preventives for large-scale human trials. Moreover, our observations bring much needed clarity to the null results of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) and set a new research priority: testing whether men with low, suboptimal selenium levels less than 0.8 ppm in toenails can achieve cancer risk reduction through daily supplementation.
机译：我们在犬类中的工作表明，硒状态与前列腺DNA损伤之间呈U型剂量反应，与男性饮食中硒与前列腺癌风险之间的关系显着相似，这表明硒含量不一定更高。在本文中，我们扩展了犬的工作，以显示使前列腺DNA损伤最小化的硒剂量也使凋亡最大化（一种由前列腺上皮细胞使用的抑制癌症的死亡开关）。这些具有启发性的发现提出了关于硒如何降低癌症风险的新思路。中等剂量的硒状态（脚趾甲中的.67-.92 ppm）有利于我们称之为“体内稳态清洁”的过程-一种上调的凋亡，优先清除受损的前列腺细胞。同样，基于通过补充硒降低其癌症风险的可能性，U型关系为将个体分层为硒反应性或硒难治性提供了有价值的见解。通过研究成年狗，这是唯一的自发性前列腺癌的非人类动物模型，我们建立了一种强大的实验方法，弥合了实验室研究和人类研究之间的空白，可以帮助定义大规模人类试验的最佳癌症预防剂量。此外，我们的观察结果非常清楚了硒和维生素E癌症预防试验（SELECT）的无效结果，并设定了新的研究重点：测试脚趾甲中硒含量低于0.8 ppm的低，次优硒的男性是否可以达到罹患癌症的风险通过每日补充减少。

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