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高传能重离子径迹上 DNA 损伤反应蛋白焦点的空间动力学。

Spatial dynamics of DNA damage response protein foci along the ion trajectory of high-LET particles.

机构信息

Physik Department E12, Technische Universität München, 85748 Garching, Germany.

出版信息

Radiat Res. 2011 Dec;176(6):706-15. doi: 10.1667/rr2592.1. Epub 2011 Jul 28.

DOI:10.1667/rr2592.1
PMID:21797665
Abstract

High-linear energy transfer (LET) ion irradiation of cell nuclei induces complex and severe DNA lesions, and foci of repair proteins are formed densely along the ion trajectory. To efficiently discriminate the densely distributed/overlapping foci along the ion trajectory, a focus recognition algorithm called FociPicker3D based on a local fraction thresholding technique was developed. We analyzed high-resolution 3D immunofluorescence microscopic focus images and obtained the kinetics and spatial development of γ-H2AX, 53BP1 and phospho-NBS1 foci in BJ1-hTERT cells irradiated with 55 MeV carbon ions and compared the results with the dynamics of double-strand break (DSB) distributions simulated using the PARTRAC model. Clusters consisting of several foci were observed along the ion trajectory after irradiation. The spatial dynamics of the protein foci supports that the foci clusters are not formed by neighboring foci but instead originate from the DSB cluster damage induced by high-LET radiations.

摘要

高线性能量转移(LET)离子照射细胞核会引起复杂而严重的 DNA 损伤,并且沿着离子轨迹密集形成修复蛋白焦点。为了有效地沿着离子轨迹区分密集分布/重叠的焦点,开发了一种称为 FociPicker3D 的焦点识别算法,该算法基于局部分数阈值技术。我们分析了高分辨率的 3D 免疫荧光焦点图像,并获得了用 55 MeV 碳离子照射的 BJ1-hTERT 细胞中 γ-H2AX、53BP1 和磷酸化-NBS1 焦点的动力学和空间发展,并将结果与使用 PARTRAC 模型模拟的双链断裂(DSB)分布的动力学进行了比较。照射后,在离子轨迹上观察到由几个焦点组成的簇。蛋白焦点的空间动力学表明,焦点簇不是由相邻焦点形成的,而是由高 LET 辐射引起的 DSB 簇损伤引起的。

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