Dose-dependence, sex- and tissue-specificity, and persistence of radiation-induced genomic DNA methylation changes
Dose-dependence, sex- and tissue-specificity, and persistence of radiation-induced genomic DNA methylation changes
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DOI：
10.1016/j.bbrc.2004.06.081
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发表时间：
2004-08-06
影响因子：
3.1
通讯作者：
Kovalchuk, O
中科院分区：
文献类型：
--
作者：
Pogribny, I;Raiche, J;Kovalchuk, O
辐射是一种众所周知的遗传毒性剂和人类致癌物质，会产生各种长期影响。它对细胞功能的有害影响目前正在积极研究。电离辐射的长期影响之一是跨代基因组不稳定性，这是分析最多但了解最少的。基因组不稳定性的遗传表明可能涉及表观遗传机制。例如位于CpG二核苷酸内的胞嘧啶残基的甲基化的变化。在本研究中，我们评估了辐射诱导的全球基因组DNA甲基化变化的剂量依赖性。我们还分析了急性和慢性高剂量（5戈伊）暴露对雄性和雌性小鼠肝、脾和肺组织DNA甲基化的影响，并评估了辐射诱导的DNA甲基化变化的可能持续性。在这里，我们报告说，辐射诱导的DNA甲基化的变化是性别和组织特异性，剂量依赖性，和持久性。同时，我们研究了暴露组织中DNA损伤的水平。基于DNA甲基化水平与DNA损伤之间的相关性，我们提出辐射诱导的全基因组DNA低甲基化与DNA修复有关。(C)2004爱思唯尔公司All rights reserved.
Radiation is a well-known genotoxic agent and human carcinogen that gives rise to a variety of long-term effects. Its detrimental influence on cellular function is actively studied nowadays. One of the most analyzed, yet least understood long-term effects of ionizinsi radiation is transgenerational genomic instability. The inheritance of genomic instability suggests the possible involvement of epigenetic mechanisms. such as changes of the methylation of cytosine residues located within CpG dinucleotides. In the current study we evaluated the dose-dependence of the radiation-induced global genome DNA methylation changes. We also analyzed the effects of acute and chronic high dose (5 Gy) exposure on DNA methylation in liver, spleen, and lung tissues of male and female mice and evaluated the possible persistence of the radiation-induced DNA methylation changes. Here we report that radiation-induced DNA methylation changes were sex- and tissue-specific, dose-dependent, and persistent. In parallel we have Studied the levels of DNA damage in the exposed tissues. Based on the correlation between the levels of DNA methylation and DNA damage we propose that radiation-induced global genome DNA hypomethylation is DNA repair-related. (C) 2004 Elsevier Inc. All rights reserved.