Lee Jae-Ho, Choi In-Jang, Song Dae-Kyu, Kim Dae-Kwang
Department of Anatomy, Keimyung University School of Medicine, 194 Dongsan-dong, Jung-gu, Daegu, 700-712, South Korea.
Cancer Genet Cytogenet. 2010 Jan 1;196(1):83-8. doi: 10.1016/j.cancergencyto.2009.09.002.
Hypoxia, one of the key tumor microenviromental factors, promotes genetic instability, which is the hallmark of human cancers. Many recent studies have demonstrated that hypoxia by itself can lead to conditions that elevate mutagenesis and inhibit the DNA repair process in cancer. The aim of this study was to investigate the cytogenetic damage and DNA repair functions in human peripheral lymphocytes exposed to hypoxia by means of sister chromatid exchange and nuclear and mitochondrial microsatellite instability (nMSI and mtMSI), respectively. Primary lymphocyte cultures obtained from blood samples of 40 healthy donors were exposed to hypoxia for 12 and 24 hours. Genomic DNA was then isolated from the fixed lymphocytes to analyze the DNA repair process by nMSI and mtMSI. The present results revealed gradual increases in SCE for both exposure times, compared to the controls, but there was no significant correlation between hypoxia and MSI. The SCE assay showed that hypoxia by itself may induce mutagenesis by causing DNA damage in normal cells. However, the DNA repair function through MSI analysis was intact.
缺氧是关键的肿瘤微环境因素之一，可促进基因不稳定，而基因不稳定是人类癌症的标志。最近许多研究表明，缺氧本身可导致诱变条件增加并抑制癌症中的DNA修复过程。本研究的目的是分别通过姐妹染色单体交换以及核和线粒体微卫星不稳定性（nMSI和mtMSI）来研究暴露于缺氧环境下的人外周血淋巴细胞的细胞遗传学损伤和DNA修复功能。从40名健康供体的血液样本中获得的原代淋巴细胞培养物暴露于缺氧环境12小时和24小时。然后从固定的淋巴细胞中分离基因组DNA，通过nMSI和mtMSI分析DNA修复过程。目前的结果显示，与对照组相比，两个暴露时间的姐妹染色单体交换均逐渐增加，但缺氧与微卫星不稳定性之间无显著相关性。姐妹染色单体交换试验表明，缺氧本身可能通过在正常细胞中造成DNA损伤而诱导诱变。然而，通过微卫星不稳定性分析的DNA修复功能是完整的。
