Schrauzer G N
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92093.
Biol Trace Elem Res. 1992 Apr-Jun;33:51-62. doi: 10.1007/BF02783992.
Selenium is increasingly recognized as a versatile anticarcinogenic agent. Its protective functions cannot be solely attributed to the action of glutathione peroxidase. Instead, selenium appears to operate by several mechanisms, depending on dosage and chemical form of selenium and the nature of the carcinogenic stress. In a major protective function, selenium is proposed to prevent the malignant transformation of cells by acting as a "redox switch" in the activation-inactivation of cellular growth factors and other functional proteins through the catalysis of oxidation-reduction reactions of critical SH groups of SS bonds. The growth-modulatory effects of selenium are dependent on the levels of intracellular GSH and the oxygen supply. In general, growth inhibition is achieved by the Se-mediated stimulation of cellular respiration. Selenium appears to inhibit the replication of tumor viruses and the activation of oncogenes by similar mechanisms. However, it may also alter carcinogen metabolism and protect DNA against carcinogen-induced damage. In additional functions of relevance to its anticarcinogenic activity, selenium acts as an acceptor of biogenic methyl groups, and is involved in the detoxification of metals and of certain xenobiotics. In its interactions with transformed cells at higher concentrations, it may induce effects ranging from metabolic and phenotypical changes, and partial renormalization to selective cytotoxicity owing to reversible or irreversible inhibition of protein and DNA synthesis. Selenium also has immunopotentiating properties. It is required for optimal macrophage and NK cell function. Its protective effects are influenced by synergistic and antagonistic dietary and environmental factors. The latter include a variety of toxic heavy metals and xenobiotic compounds, but they are also influenced by essential elements, such as zinc. The exposure to antagonistic factors must be minimized for the full expression of its anticarcinogenic potential.
硒越来越被认为是一种多功能的抗癌剂。其保护功能不能仅仅归因于谷胱甘肽过氧化物酶的作用。相反，硒似乎通过多种机制起作用，这取决于硒的剂量、化学形式以及致癌应激的性质。在一项主要的保护功能中，有人提出硒通过在细胞生长因子和其他功能蛋白的激活 - 失活过程中充当“氧化还原开关”来防止细胞的恶性转化，这一过程是通过催化关键的SH基团或SS键的氧化还原反应实现的。硒的生长调节作用取决于细胞内谷胱甘肽（GSH）的水平和氧气供应。一般来说，通过硒介导的细胞呼吸刺激可实现生长抑制。硒似乎通过类似机制抑制肿瘤病毒的复制和癌基因的激活。然而，它也可能改变致癌物代谢并保护DNA免受致癌物诱导的损伤。在与其抗癌活性相关的其他功能中，硒作为生物甲基基团的受体，参与金属和某些外源性物质的解毒。在高浓度下与转化细胞相互作用时，由于对蛋白质和DNA合成的可逆或不可逆抑制，它可能诱导从代谢和表型变化、部分正常化到选择性细胞毒性等一系列效应。硒还具有免疫增强特性。它是巨噬细胞和自然杀伤细胞（NK细胞）发挥最佳功能所必需的。其保护作用受到协同和拮抗的饮食及环境因素的影响。后者包括各种有毒重金属和外源性化合物，但它们也受到锌等必需元素的影响。为了充分发挥其抗癌潜力，必须尽量减少接触拮抗因素。
