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首页> 外文期刊>Radiation and Environmental Biophysics >Alteration of mtDNA copy number, mitochondrial gene expression and extracellular DNA content in mice after irradiation at lethal dose
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Alteration of mtDNA copy number, mitochondrial gene expression and extracellular DNA content in mice after irradiation at lethal dose

机译：致死剂量照射后小鼠线粒体DNA拷贝数，线粒体基因表达和细胞外DNA含量的变化

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摘要

High steady-state transcriptional activity is essential for normal mitochondrial function. The requisite transcription rate is satisfied in part by high copy number of mitochondrial DNA (mtDNA). In the present study, we analyze mtDNA copy number by real-time PCR in nucleated blood cells from control mice and mice exposed to 1- or 10-Gy X-radiation. Transcription of the oxidative phosphorylation-associated genes cytb, atp6, nd4, nd2 and d-loop region was monitored in these nucleated blood cells similarly by real-time PCR. We observed a 50% decrease in the ratio of mitochondrial to nuclear DNA (mtDNA/ nDNA) in blood cells, while the mtDNADNA ratio in serum increased. After a lethal 10-Gy dose of X-irradia-tion, we observed an 80% decrease in the number of circulating lymphocytes. In response to a 10-Gy radiation dose, we observed transiently increased mtDNADNA ratio and transcription within the initial 5 h post-treatment. At 24-72 h, the mtDNADNA ratio in surviving cells was reduced to the level observed in blood cells irradiated with 1 Gy. We observed a decrease in the serum mtDNADNA ratio due to an increase in nDNA content rather than a decrease in mtDNA. Taken together, results presented herein suggest that the mtDNADNA ratio may be of clinical value potentially as a diagnostic tool, particularly in oncology patients undergoing radiation therapy.
机译：高稳态转录活性对于正常的线粒体功能至关重要。线粒体DNA（mtDNA）的高拷贝数可以部分满足所需的转录速率。在本研究中，我们通过实时PCR分析来自对照小鼠和暴露于1或10-Gy X射线辐射的小鼠的有核血细胞中的mtDNA拷贝数。氧化磷酸化相关基因cytb，atp6，nd4，nd2和d环区域的转录也通过实时PCR监测了这些有核血细胞。我们观察到血细胞中线粒体与核DNA（mtDNA / nDNA）的比率降低了50％，而血清中mtDNA / nDNA的比率却增加了。致命的10 Gy剂量的X射线照射后，我们观察到循环淋巴细胞的数量减少了80％。响应10 Gy辐射剂量，我们观察到在治疗后的最初5小时内mtDNA / nDNA比率和转录瞬时增加。在24-72小时，存活细胞中的mtDNA / nDNA比值降低到用1 Gy照射的血细胞中观察到的水平。我们观察到血清mtDNA / nDNA比率的降低是由于nDNA含量的增加而不是mtDNA的降低。两者合计，本文呈现的结果表明，mtDNA / nDNA比率可能具有作为诊断工具的临床价值，尤其是在接受放射疗法的肿瘤患者中。

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