Harrison P R, Lanfear J, Wu L, Fleming J, McGarry L, Blower L
Beatson Institute for Cancer Research, CRC Beatson Laboratories, Glasgow, Scotland, UK.
Biomed Environ Sci. 1997 Sep;10(2-3):235-45.
There is very convincing evidence that a high dietary level of selenium substantially reduces the incidence of a wide variety of animal cancers. The human epidemiological evidence is less clear cut, but overall suggests that selenium may be protective: the evidence is strongest in men in relation to gastro-intestinal cancers. There is evidence that dietary selenium compounds reduce the formation of DNA adducts by carcinogens. Selenium compounds also inhibit growth in vitro and induce apoptosis. In general, there is a good correlation between the effectiveness of selenium compounds in chemoprevention and growth inhibition, implying that the mechanisms of growth inhibition and chemoprevention may be similar and that a major factor in the chemopreventive effects of selenium compounds in vivo is their ability to retard outgrowth of pre-malignant cells. Various hypotheses have been advanced as to how selenium compounds might prevent tumour cell growth. One is that they cause apoptosis by inducing oxidative stress. However, we have shown that the most potent selenium compound, selenodiglutathione (SDG), a natural metabolite of selenite, does not induce oxidative stress, at least not in the same way as other oxidants such as H2O2 and diamide. Firstly, a partially selenium-resistant variant cell line does not show increased resistance to H2O2. Moreover, SDG does not induce widespread tyrosine phosphorylation, including MAP and SAP kinases, like other oxidants such as H2O2 and diamide and its effects are not reversed by pretreatment with the tyrosine kinase inhibitor, herbimycin. Our experiments with the selenium-resistant variant suggest that a novel selenium-binding protein may be involved in growth inhibition by selenium.
有非常令人信服的证据表明，高膳食水平的硒能大幅降低多种动物癌症的发病率。人类流行病学证据不太明确，但总体表明硒可能具有保护作用：在男性中，与胃肠道癌症相关的证据最为确凿。有证据表明，膳食中的硒化合物可减少致癌物形成DNA加合物。硒化合物还能在体外抑制生长并诱导细胞凋亡。一般来说，硒化合物在化学预防和生长抑制方面的有效性之间存在良好的相关性，这意味着生长抑制和化学预防的机制可能相似，并且硒化合物在体内化学预防作用的一个主要因素是它们延缓癌前细胞生长的能力。关于硒化合物如何预防肿瘤细胞生长，已经提出了各种假说。一种假说是它们通过诱导氧化应激导致细胞凋亡。然而，我们已经表明，最有效的硒化合物亚硒酸二谷胱甘肽（SDG），一种亚硒酸盐的天然代谢产物，不会诱导氧化应激，至少不像其他氧化剂如过氧化氢（H2O2）和二酰胺那样。首先，一种部分抗硒的变异细胞系对H2O2并没有表现出更高的抗性。此外，SDG不会像其他氧化剂如H2O2和二酰胺那样诱导广泛的酪氨酸磷酸化，包括丝裂原活化蛋白激酶（MAP）和应激激活蛋白激酶（SAP），并且其作用不会被酪氨酸激酶抑制剂除莠霉素预处理所逆转。我们用抗硒变异体进行的实验表明，一种新型的硒结合蛋白可能参与了硒对生长的抑制作用。
