Alam Mohammad Rizwan, Kim Dae-Kwang
Department of Medical Genetics, School of Medicine, Keimyung University, Daegu, Republic of Korea.
Hanvit Institute for Medical Genetics, Daegu, Republic of Korea.
Toxicol Rep. 2020 Oct 17;7:1443-1447. doi: 10.1016/j.toxrep.2020.10.011. eCollection 2020.
Hypoxia is related to a variety of diseases, such as cardiovascular and inflammatory diseases and various cancers. Telomere length (TL) may vary according to the hypoxia level and cell types. To the best of our knowledge, no study has investigated the effect of moderate hypoxia on TL and mitochondrial DNA copy number (mtDNAcn) in human lymphocytes. Therefore, in this study, we analyzed the effect of moderate hypoxia on TL in correlation with mtDNAcn. This study included 32 healthy male nonsmoker's subjects; in this cohort, we had previously studied sister chromatid exchange and microsatellite instability. Blood samples from each subject were divided into three groups: a control group and two experimental groups exposed to moderate hypoxia for 12 or 24 h. Relative TL and mtDNAcn were measured by a quantitative real-time polymerase chain reaction. The TL in the control group did not significantly differ from that in the experimental group subjected to hypoxia for 12 h; however, the TL in the 24 h hypoxia-treated experimental group was significantly higher than that in the control group. The correlation between TL and mtDNAcn was not statistically significant in the two hypoxic states. The increase in TL was observed on exposure to hypoxia for 24 h and not for 12 h; thus, the findings suggest that telomere elongation is related to hypoxia exposure duration. The mtDNAcn in the two experimental groups did not significantly differ from that in the control group. These observations suggest that mtDNAcn alterations show more genetic stability than TL alterations. To the best of our knowledge, this is the first study on human lymphocytes reporting an increase in TL and no alteration in mtDNAcn after short-time exposure to moderate hypoxia.
缺氧与多种疾病相关,如心血管疾病、炎症性疾病及各类癌症。端粒长度(TL)可能会因缺氧水平和细胞类型的不同而有所变化。据我们所知,尚无研究探讨中度缺氧对人淋巴细胞中端粒长度(TL)和线粒体DNA拷贝数(mtDNAcn)的影响。因此,在本研究中,我们分析了中度缺氧对TL的影响及其与mtDNAcn的相关性。本研究纳入了32名健康男性非吸烟者;在该队列中,我们之前研究过姐妹染色单体交换和微卫星不稳定性。每位受试者的血样被分为三组:一个对照组和两个暴露于中度缺氧12小时或24小时的实验组。通过定量实时聚合酶链反应测量相对TL和mtDNAcn。对照组的TL与缺氧12小时的实验组相比无显著差异;然而,缺氧处理24小时的实验组的TL显著高于对照组。在两种缺氧状态下,TL与mtDNAcn之间的相关性无统计学意义。观察到在缺氧24小时而非12小时时TL增加;因此,研究结果表明端粒延长与缺氧暴露持续时间有关。两个实验组的mtDNAcn与对照组相比无显著差异。这些观察结果表明,mtDNAcn的改变比TL的改变显示出更高的遗传稳定性。据我们所知,这是第一项关于人淋巴细胞的研究,报道了短期暴露于中度缺氧后端粒长度增加而mtDNAcn无改变。