Seo Young R, Sweeney Christopher, Smith Martin L
Indiana University Cancer Center, Department of Microbiology, Walther Oncology Center, Indiana University School of Medicine and Walther Cancer Institute, Indianapolis, IN 46202, USA.
Oncogene. 2002 May 23;21(23):3663-9. doi: 10.1038/sj.onc.1205468.
Selenium compounds have a long history in chemoprevention of mammary and colon cancers in rodent models. Selenium compounds are in current clinical trials, having shown promise in prevention of prostate and other human cancers. In human tissues, it has been estimated that each cell sustains approximately 10 000 potentially mutagenic (if not repaired) lesions per day due to endogenous DNA damage. Almost no studies have addressed the potential for selenium compounds to induce DNA repair, a potential mechanism for their cancer-preventive actions. We show that selenium in the form of selenomethionine induces a DNA repair response in normal human fibroblasts in vitro, and protects cells from DNA damage. We show a possible mechanism for the inducible DNA repair response, in which enhanced repair complex formation was observed in selenomethionine-treated cells.
在啮齿动物模型中，硒化合物在乳腺癌和结肠癌的化学预防方面有着悠久的历史。目前硒化合物正处于临床试验阶段，已显示出在预防前列腺癌和其他人类癌症方面的前景。据估计，在人体组织中，由于内源性DNA损伤，每个细胞每天大约会承受10000个潜在的诱变（若不修复）损伤。几乎没有研究探讨过硒化合物诱导DNA修复的可能性，而这是其癌症预防作用的一种潜在机制。我们发现，硒代蛋氨酸形式的硒在体外可诱导正常人成纤维细胞产生DNA修复反应，并保护细胞免受DNA损伤。我们还展示了诱导性DNA修复反应的一种可能机制，即在经硒代蛋氨酸处理的细胞中观察到修复复合物形成增强。
