Visualization of complex DNA double-strand breaks in a tumor treated with carbon ion radiotherapy.

Visualization of complex DNA double-strand breaks in a tumor treated with carbon ion radiotherapy.
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DOI:
10.1038/srep22275
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发表时间:
2016-03-01
期刊:
影响因子:
4.6
通讯作者:
Nakano T
Nakano T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Oike T;Niimi A;Okonogi N;Murata K;Matsumura A;Noda SE;Kobayashi D;Iwanaga M;Tsuchida K;Kanai T;Ohno T;Shibata A;Nakano T

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碳离子放射治疗在治疗x射线耐药肿瘤方面显示出巨大的潜力。基础研究表明,碳离子诱导的强细胞杀伤作用是基于它们引起复杂DNA双链断裂(DSBs)的能力。然而,缺乏证据支持在实际患者中形成复杂的dsb。在这里,我们使用先进的高分辨率显微镜和反褶积来显示复杂的dsb在临床接受碳离子放疗的人类肿瘤中形成,但在接受x射线放疗的肿瘤中没有形成。此外,使用物理模型的分析表明,放射治疗引起的DSBs的复杂性与线性能量转移有关,碳离子束的线性能量转移远高于x射线。临床标本中复杂dsb的可视化将有助于我们了解碳离子放疗的抗肿瘤作用。
Carbon ion radiotherapy shows great potential as a cure for X-ray-resistant tumors. Basic research suggests that the strong cell-killing effect induced by carbon ions is based on their ability to cause complex DNA double-strand breaks (DSBs). However, evidence supporting the formation of complex DSBs in actual patients is lacking. Here, we used advanced high-resolution microscopy with deconvolution to show that complex DSBs are formed in a human tumor clinically treated with carbon ion radiotherapy, but not in a tumor treated with X-ray radiotherapy. Furthermore, analysis using a physics model suggested that the complexity of radiotherapy-induced DSBs is related to linear energy transfer, which is much higher for carbon ion beams than for X-rays. Visualization of complex DSBs in clinical specimens will help us to understand the anti-tumor effects of carbon ion radiotherapy.