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首页> 外文期刊>Environmental Epigenetics >Fractionated low-dose exposure to ionizing radiation leads to DNA damage, epigenetic dysregulation, and behavioral impairment
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Fractionated low-dose exposure to ionizing radiation leads to DNA damage, epigenetic dysregulation, and behavioral impairment

机译：小剂量的小剂量暴露于电离辐射会导致DNA损伤，表观遗传失调和行为障碍

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Studies of F ractionated E xposure to L ow D oses of I onizing R adiation (FELDIR) has become of increasing importance to clinical interventions. Its consequences on DNA damage, physical, and mental health have been insufficiently investigated, however. The goal of this study was to determine the effects of FELDIR on the brain using a mouse model. We addressed the levels of DNA damage, global genomic methylation, and DNA methylation machinery in cerebellum, frontal lobe, olfactory bulb and hippocampal tissues, as well as behavioral changes linked to FELDIR exposure. The results reveal increased levels of DNA damage, as reflected by increased occurrence of DNA S trand B reaks (SBs) and dysregulation of stress-response kinase p38. FELDIR also resulted in initial loss of global genomic methylation and altered expression of methyltransferases DNMT1 (down-regulation) and DNMT3a (up-regulation), as well as methyl-binding protein MeCP2 (up-regulation). FELDIR-associated behavioral changes included impaired skilled limb placement on a ladder rung task, increased rearing activity in an open field, and elevated anxiety-like behaviors. The said alterations showed significant dose and tissue specificity. Thus, FELDIR represents a critical impact on DNA integrity and behavioral outcomes that need to be considered in the design of clinical intervention studies.
机译：对低剂量离子化作用（FELDIR）进行分装的研究在临床干预中变得越来越重要。但是，其对DNA损伤，身体和心理健康的影响尚未得到充分研究。这项研究的目的是使用小鼠模型确定FELDIR对大脑的影响。我们研究了小脑，额叶，嗅球和海马组织中DNA损伤，整体基因组甲基化和DNA甲基化机制的水平，以及与FELDIR暴露相关的行为变化。结果表明，DNA损伤水平增加，这反映为DNA S trand B reak（SBs）的发生增加和应激反应激酶p38的失调。 FELDIR还导致全球基因组甲基化的最初丧失，甲基转移酶DNMT1（下调）和DNMT3a（上调）以及甲基结合蛋白MeCP2（上调）的表达发生了改变。与FELDIR相关的行为改变包括：熟练的肢体放置在梯级梯级任务上受损，在空旷地中增加饲养活动以及类似焦虑的行为升高。所述改变显示出显着的剂量和组织特异性。因此，FELDIR代表了对DNA完整性和行为结果的关键影响，在临床干预研究的设计中需要考虑这些影响。

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