Replication of murine mitochondrial DNA following irradiation.

Replication of murine mitochondrial DNA following irradiation.
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DOI:
10.1007/978-0-387-85998-9_7
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发表时间:
2009
影响因子:
--
通讯作者:
Okunieff, Paul
Okunieff, Paul
中科院分区:
医学4区
文献类型:
--
作者:
Zhang, Hengshan;Maguire, David;Swarts, Steven;Sun, Weimin;Yang, Shanmin;Wang, Wei;Liu, Chaomei;Zhang, Mei;Zhang, Di;Zhang, Louie;Zhang, Kunzhong;Keng, Peter;Zhang, Lurong;Okunieff, Paul

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辐射对体内线粒体基因组的影响在很大程度上是未知的。虽然线粒体DNA(MtDNA)对细胞的生存和增殖至关重要,但与核DNA(NDNA)相比,它几乎没有DNA修复机制。更好地了解辐射是如何影响线粒体DNA的,应该会带来辐射防护的新方法。我们开发了一种使用实时荧光定量聚合酶链式反应的新系统,它能灵敏地检测mtDNA与nDNA相比拷贝数的变化。在每个样本中,编码18S rRNA的DNA序列在与mtDNA序列同时运行时作为nDNA参考。2Gy4Gy全身照射(TBI)后24小时收集的小鼠小肠mtDNA水平较对照组升高。4Gy剂量比2Gy产生更大的效应。类似地,在4Gy或7GyTBI后24小时收集的骨髓中,7Gy产生的反应比4Gy强。作为时间的函数,48小时比24小时的影响更大。综上所述,我们发现辐射增加了mtDNA/NDNA的比例,并且这种影响似乎是组织独立的,并且似乎随着辐射剂量和辐射暴露后的时间而增加。
The effect of radiation on the mitochondrial genome in vivo is largely unknown. Though mitochondrial DNA (mtDNA) is vital for cellular survival and proliferation, it has little DNA repair machinery compared with nuclear DNA (nDNA). A better understanding of how radiation affects mtDNA should lead to new approaches for radiation protection. We have developed a new system using real-time PCR that sensitively detects the change in copy number of mtDNA compared with nDNA. In each sample, the DNA sequence coding 18S rRNA served as the nDNA reference in a run simultaneously with a mtDNA sequence. Small bowel collected 24 hours after 2 Gy or 4 Gy total body irradiation (TBI) exhibited increased levels of mtDNA compared with control mice. A 4 Gy dose produced a greater effect than 2 Gy. Similarly, in bone marrow collected 24 hours after 4 Gy or 7 Gy TBI, 7 Gy produced a greater response than 4 Gy. As a function of time, a greater effect was seen at 48 hours compared with 24 hours. In conclusion, we found that radiation increased the ratio of mtDNA:nDNA and that this effect seems to be tissue independent and seems to increase with radiation dose and duration following radiation exposure.
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