Imaging features that discriminate between foci induced by high- and low-LET radiation in human fibroblasts
Imaging features that discriminate between foci induced by high- and low-LET radiation in human fibroblasts
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DOI：
10.1667/rr3538.1
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发表时间：
2006-05-01
影响因子：
3.4
通讯作者：
Barcellos-Hoff, MH
中科院分区：
文献类型：
--
作者：
Costes, SV;Boissière, A;Barcellos-Hoff, MH
在这项研究中，我们研究了辐射诱导的病灶的形成在正常人成纤维细胞暴露于X射线或130 keV/μ m氮离子使用磷酸化蛋白激酶共济失调毛细血管扩张突变（ATMP）和组蛋白H2 AX（γ-H2 AX）的抗体。高内容的自动图像分析被用来量化辐射诱导的病灶的免疫荧光。氮离子照射后2小时内，两种蛋白质的辐射诱导病灶的大小增加，而暴露于低LET辐射后，辐射诱导病灶的大小没有变化。辐射诱导的ATMp病灶的数量在X射线暴露后显示出更快的上升和更高的频率，并且更快地被解决，使得辐射诱导的病灶的频率降低了90%，相比之下，在30 cGy后暴露于高LET辐射2小时后降低了60%。相比之下，辐射诱导的γ-H2 AX焦点形成的动力学对于高LET辐射和低LET辐射是相似的，因为它在早期达到平台并保持恒定长达2小时。辐射诱导的γ-H2 AX焦点的高分辨率3D图像和剂量学计算表明，氮离子的多个双链断裂包含在4.4 Mbp的大核域内。我们的工作表明，辐射诱导的病灶的大小和频率作为辐射质量，剂量，时间和蛋白质靶的函数而变化。因此，即使双链断裂和辐射诱发的病灶是相关的，两者的动态性质与它们在低剂量不同辐射质量下的公认等效性相矛盾。(c)2006年，辐射研究协会。
In this study, we investigated the formation of radiation-induced foci in normal human fibroblasts exposed to X rays or 130 keV/mu m nitrogen ions using antibodies to phosphorylated protein kinase ataxia telangiectasia mutated (ATMp) and histone H2AX (gamma-H2AX). High-content automatic image analysis was used to quantify the immunofluorescence of radiation-induced foci. The size of radiation-induced foci increased for both proteins over a 2-h period after nitrogen-ion irradiation, while the size of radiation-induced foci did not change after exposure to low-LET radiation. The number of radiation-induced ATMp foci showed a more rapid rise and greater frequency after X-ray exposure and was resolved more rapidly such that the frequency of radiation-induced foci decreased by 90% compared to 60% after exposure to high-LET radiation 2 h after 30 cGy. In contrast, the kinetics of radiation-induced gamma-H2AX focus formation was similar for high- and low-LET radiation in that it reached a plateau early and remained constant for up to 2 h. High-resolution 3D images of radiation-induced gamma-H2AX foci and dosimetry computation suggest that multiple double-strand breaks from nitrogen ions are encompassed within large nuclear domains of 4.4 Mbp. Our work shows that the size and frequency of radiation-induced foci vary as a function of radiation quality, dose, time and protein target. Thus, even though double-strand breaks and radiation-induced foci are correlated, the dynamic nature of both contradicts their accepted equivalence for low doses of different radiation qualities. (c) 2006 by Radiation Research Society.