Efficient Rejoining of DNA Double-Strand Breaks despite Increased Cell-Killing Effectiveness following Spread-Out Bragg Peak Carbon-Ion Irradiation.
Efficient Rejoining of DNA Double-Strand Breaks despite Increased Cell-Killing Effectiveness following Spread-Out Bragg Peak Carbon-Ion Irradiation.
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DOI：
10.3389/fonc.2016.00028
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发表时间：
2016
影响因子：
4.7
通讯作者：
Taucher-Scholz G
中科院分区：
文献类型：
--
作者：
Averbeck NB;Topsch J;Scholz M;Kraft-Weyrather W;Durante M;Taucher-Scholz G
与光子疗法相比，用带电粒子对实体肿瘤进行放射疗法具有几个优点;其中包括肿瘤中的适形剂量分布、改善肿瘤周围健康组织的保留以及在离子比质子重的情况下肿瘤靶体积中的相对生物学有效性（RBE）增加。生物学效应的一个重要因素是DNA损伤，其中DNA双链断裂（DSB）是最有害的。这些损伤的可修复性决定了照射后的细胞存活率，从而决定了RBE。有趣的是，使用磷酸化H2 AX作为DSB标记物，我们在人成纤维细胞中的数据显示，在用碳离子进行治疗相关的扩散布拉格峰照射后，DSB非常有效地重新连接，尽管细胞存活的RBE增加。这表明，在重离子辐射的RBE增加中，错误修复起着重要的作用。将讨论错误修复的可能来源。
Radiotherapy of solid tumors with charged particles holds several advantages in comparison to photon therapy; among them conformal dose distribution in the tumor, improved sparing of tumor-surrounding healthy tissue, and an increased relative biological effectiveness (RBE) in the tumor target volume in the case of ions heavier than protons. A crucial factor of the biological effects is DNA damage, of which DNA double-strand breaks (DSBs) are the most deleterious. The reparability of these lesions determines the cell survival after irradiation and thus the RBE. Interestingly, using phosphorylated H2AX as a DSB marker, our data in human fibroblasts revealed that after therapy-relevant spread-out Bragg peak irradiation with carbon ions DSBs are very efficiently rejoined, despite an increased RBE for cell survival. This suggests that misrepair plays an important role in the increased RBE of heavy-ion radiation. Possible sources of erroneous repair will be discussed.