Alpha particles induce pan-nuclear phosphorylation of H2AX in primary human lymphocytes mediated through ATM
Alpha particles induce pan-nuclear phosphorylation of H2AX in primary human lymphocytes mediated through ATM
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DOI：
10.1016/j.bbamcr.2015.06.010
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发表时间：
2015-10-01
影响因子：
5.1
通讯作者：
Prise, Kevin
中科院分区：
文献类型：
--
作者：
Horn, Simon;Brady, Darren;Prise, Kevin
在过去十年中，以重离子束线中的碳离子形式或在新的放射性核素治疗中以α粒子形式使用高线性能量转移辐射的情况已大大增加，并且由于与传统治疗相比，它们可以提供有利的剂量分布，因此将继续这样做。先前已有研究表明，暴露于重离子可诱导几种DNA修复蛋白（如H2AX和ATM）的泛核磷酸化。在这里，我们描述了α粒子对体外辐照的原代人外周血淋巴细胞的类似作用。在α粒子照射下，整个细胞核中观察到H2AX和ATM泛核磷酸化，但DNA-PK和53BP1未被磷酸化。抑制ATM，而非DNA-PK，导致α粒子照射淋巴细胞中H2AX泛核磷酸化的丧失。泛核γ - h2ax信号在24小时内迅速丢失，其丢失速率远远大于焦点丢失速率。令人惊讶的是，泛核γ - h2ax强度不依赖于α粒子诱导的双链断裂的数量，而是依赖于穿过细胞核的α粒子的数量。粒子辐射的这种独特的依赖于影响的损伤特征在放射防护和临床肿瘤学领域确定放射性核素生物剂量学方面都很重要，并可能指示患者对新的放射性核素癌症治疗的反应。(C) 2015 Elsevier B.V.版权所有
The use of high linear energy transfer radiations in the form of carbon ions in heavy ion beam lines or alpha particles in new radionuclide treatments has increased substantially over the past decade and will continue to do so due to the favourable dose distributions they can offer versus conventional therapies. Previously it has been shown that exposure to heavy ions induces pan-nuclear phosphorylation of several DNA repair proteins such as H2AX and ATM in vitro. Here we describe similar effects of alpha particles on ex vivo irradiated primary human peripheral blood lymphocytes. Following alpha particle irradiation pan-nuclear phosphorylation of H2AX and ATM, but not DNA-PK and 53BP1, was observed throughout the nucleus. Inhibition of ATM, but not DNA-PK, resulted in the loss of pan-nuclear phosphorylation of H2AX in alpha particle irradiated lymphocytes. Pan-nuclear gamma-H2AX signal was rapidly lost over 24 h at a much greater rate than foci loss. Surprisingly, pan-nuclear gamma-H2AX intensity was not dependent on the number of alpha particle induced double strand breaks, rather the number of alpha particles which had traversed the cell nucleus. This distinct fluence dependent damage signature of particle radiation is important in both the fields of radioprotection and clinical oncology in determining radionuclide biological dosimetry and may be indicative of patient response to new radionuclide cancer therapies. (C) 2015 Elsevier B.V. All rights reserved.