A single whole-body low dose X-irradiation does not affect L1, B1 and IAP repeat element DNA methylation longitudinally.
A single whole-body low dose X-irradiation does not affect L1, B1 and IAP repeat element DNA methylation longitudinally.
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DOI：
10.1371/journal.pone.0093016
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ormsby RJ
中科院分区：
文献类型：
--
作者：
Newman MR;Sykes PJ;Blyth BJ;Bezak E;Lawrence MD;Morel KL;Ormsby RJ
低剂量辐射适应性反应已被证明对高剂量辐射以及衰老诱导的基因组不稳定具有保护作用。我们假设，单次低剂量全身照射将诱导辐射适应性反应，从而减少或消除小鼠重复元件DNA甲基化的与衰老相关的变化。在假照射或10mGyX射线照射后，连续采集外周血，用高分辨熔融分析聚合酶链式反应(PCR)扩增产物的高分辨熔融分析来评价长散布核素1(L1)、B1和脑室内A粒子(IAP)重复序列甲基化的差异。照射后420天，外周血、脾或肝脏L1、B1和IAP元素甲基化均未观察到与辐射或衰老相关的变化。对未经治疗的老年小鼠的脾和肝组织的分析表明，17-19个月龄组的小鼠表现出比年轻或老年小鼠更高的重复元件甲基化，但甲基化水平并没有随着年龄的增长而总体下降。这是第一次对低剂量辐射对小鼠外周血中重复元素甲基化的影响进行的时间分析，也是第一次研究这种剂量对辐射敏感组织(脾)和衰老过程的基础组织(肝脏)中重复元素甲基化的长期影响。我们的数据表明，小鼠DNA重复元件的甲基化可能会随着年龄的增长而波动，但与人类研究不同的是，并没有显示出与年龄相关的整体下降。此外，我们的结果表明，低剂量的电离辐射不会在研究中检查的组织和时间点诱导可检测到的小鼠重复元件DNA甲基化的变化。这一辐射剂量与人类诊断性辐射暴露有关，并表明10mGyX射线剂量与高剂量辐射不同，不会对重复元素或全球DNA甲基化造成重大的短期或长期变化。
The low dose radioadaptive response has been shown to be protective against high doses of radiation as well as aging-induced genomic instability. We hypothesised that a single whole-body exposure of low dose radiation would induce a radioadaptive response thereby reducing or abrogating aging-related changes in repeat element DNA methylation in mice. Following sham or 10 mGy X-irradiation, serial peripheral blood sampling was performed and differences in Long Interspersed Nucleic Element 1 (L1), B1 and Intracisternal-A-Particle (IAP) repeat element methylation between samples were assessed using high resolution melt analysis of PCR amplicons. By 420 days post-irradiation, neither radiation- or aging-related changes in the methylation of peripheral blood, spleen or liver L1, B1 and IAP elements were observed. Analysis of the spleen and liver tissues of cohorts of untreated aging mice showed that the 17–19 month age group exhibited higher repeat element methylation than younger or older mice, with no overall decline in methylation detected with age. This is the first temporal analysis of the effect of low dose radiation on repeat element methylation in mouse peripheral blood and the first to examine the long term effect of this dose on repeat element methylation in a radiosensitive tissue (spleen) and a tissue fundamental to the aging process (liver). Our data indicate that the methylation of murine DNA repeat elements can fluctuate with age, but unlike human studies, do not demonstrate an overall aging-related decline. Furthermore, our results indicate that a low dose of ionising radiation does not induce detectable changes to murine repeat element DNA methylation in the tissues and at the time-points examined in this study. This radiation dose is relevant to human diagnostic radiation exposures and suggests that a dose of 10 mGy X-rays, unlike high dose radiation, does not cause significant short or long term changes to repeat element or global DNA methylation.
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Baccarelli, A.