Irons Robert, Carlson Bradley A, Hatfield Dolph L, Davis Cindy D
Nutritional Science Research Group, National Cancer Institute, Rockville, MD 20852, USA.
J Nutr. 2006 May;136(5):1311-7. doi: 10.1093/jn/136.5.1311.
Selenium has cancer protective effects in a variety of experimental systems. Currently, it is not known whether selenoproteins or low molecular weight selenocompounds are responsible for this activity. To evaluate the contribution of selenoproteins to the cancer protective effects of selenium, we used transgenic mice that carry a mutant selenocysteine transfer RNA gene, which causes reduced selenoprotein synthesis. Selenium homeostasis was characterized in liver and colon of wild-type and transgenic mice fed selenium-deficient diets supplemented with 0, 0.1, or 2.0 microg selenium (as selenite)/g diet. (75)Se-labeling, Western blot analysis, and enzymatic activities revealed that transgenic mice have reduced (P < 0.05) liver and colon glutathione peroxidase expression, but conserved thioredoxin reductase expression compared with wild-type mice, regardless of selenium status. Transgenic mice had more (P < 0.05) selenium in the nonprotein fraction of the liver and colon than wild-type mice, indicating a greater amount of low molecular weight selenocompounds. Compared with wild-type mice, transgenic mice had more (P < 0.05) azoxymethane-induced aberrant crypt formation (a preneoplastic lesion for colon cancer). Supplemental selenium decreased (P < 0.05) the number of aberrant crypts and aberrant crypt foci in both wild-type and transgenic mice. These results provide evidence that a lack of selenoprotein activity increases colon cancer susceptibility. Furthermore, low molecular weight selenocompounds reduced preneoplastic lesions independent of the selenoprotein genotype. These results are, to our knowledge, the first to provide evidence that both selenoproteins and low molecular weight selenocompounds are important for the cancer-protective effects of selenium.
在多种实验系统中，硒具有抗癌作用。目前尚不清楚是硒蛋白还是低分子量硒化合物发挥了这种活性。为了评估硒蛋白对硒抗癌作用的贡献，我们使用了携带突变硒代半胱氨酸转运RNA基因的转基因小鼠，该基因会导致硒蛋白合成减少。对野生型和转基因小鼠的肝脏和结肠进行硒稳态特征分析，这些小鼠食用添加了0、0.1或2.0微克硒（以亚硒酸盐形式）/克饮食的缺硒日粮。（75）硒标记、蛋白质印迹分析和酶活性显示，无论硒状态如何，与野生型小鼠相比，转基因小鼠肝脏和结肠中的谷胱甘肽过氧化物酶表达降低（P<0.05），但硫氧还蛋白还原酶表达保持不变。转基因小鼠肝脏和结肠非蛋白部分中的硒含量比野生型小鼠更多（P<0.05），表明低分子量硒化合物含量更高。与野生型小鼠相比，转基因小鼠由氧化偶氮甲烷诱导的异常隐窝形成（结肠癌的一种癌前病变）更多（P<0.05）。补充硒可降低野生型和转基因小鼠中异常隐窝和异常隐窝灶的数量（P<0.05）。这些结果证明，缺乏硒蛋白活性会增加患结肠癌的易感性。此外，低分子量硒化合物可减少癌前病变，且与硒蛋白基因型无关。据我们所知，这些结果首次证明硒蛋白和低分子量硒化合物对硒的抗癌作用都很重要。
