Phosphorylated histone H2AX in relation to cell survival in tumor cells and xenografts exposed to single and fractionated doses of X-rays

Phosphorylated histone H2AX in relation to cell survival in tumor cells and xenografts exposed to single and fractionated doses of X-rays
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DOI:
10.1016/j.radonc.2006.07.026
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发表时间:
2006-08-01
影响因子:
5.7
通讯作者:
Olive, Peggy L.
Olive, Peggy L.
中科院分区:
医学1区
文献类型:
--
作者:
Klokov, Dmitry;MacPhail, Susan M.;Olive, Peggy L.

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背景和目的:将生长为单层或异种移植肿瘤的人肿瘤细胞系暴露于单个或多个分数的X射线,并评估使用残余γ H2AX来识别放射敏感性cells的能力。Materials and Methods:暴露于单个或每日分数的X射线后24小时,分析来自单层或异种移植的人肿瘤细胞的克隆形成存活分数。还将细胞固定并用抗γ H2AX抗体标记,用于通过流式细胞术和图像细胞术进行分析。残留γ H2AX的相对量和细胞的百分比与< 3个病灶进行了比较,与克隆存活分数测量为同一population.Results:γ H2AX的分数剩余24小时后,X射线照射后相对于峰值水平1小时后曝光与放射敏感性(SF2)为18人肿瘤细胞系。SiHa、C33A和WiDr细胞中γ H2AX灶< 3的细胞分数预测暴露于单剂量或单剂量的单层细胞的克隆形成存活分数。多达5个馏分。使用细胞从异种移植肿瘤的照射mice.Conclusion:保留γ H2AX病灶24小时后,单次或分次剂量的肿瘤细胞的百分比似乎是一个有用的措施,是潜在的适用于临床的细胞放射敏感性。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Background and purpose: Human tumor cell lines grown as monolayers or xenograft tumors were exposed to single or multiple fractions of X-rays and the ability to use residual gamma H2AX to identify radiosensitive cells was assessed.Materials and methods: Twenty-four hour after exposure to single or daily fractions of X-rays, human tumor cells from monolayers or xenografts were analyzed for clonogenic surviving fraction. Cells were also fixed and labeled with antiy-gamma H2AX antibodies for analysis by flow and image cytometry. The relative amount of residual gamma H2AX and the percentage of cells with < 3 foci were compared with the clonogenic surviving fraction measured for the same population.Results: The fraction of gamma H2AX remaining 24 h after X-irradiation relative to peak levels 1 h after exposure was correlated with radiosensitivity (SF2) for 18 human tumor cell lines. The fraction of SiHa, C33A and WiDr cells with < 3 gamma H2AX foci was predictive of clonogenic surviving fraction for both monolayer cells exposed to either single doses or. up to 5 fractions. Similar results were obtained using cells from xenograft tumors of irradiated mice.Conclusion: The percentage of tumor cells that retain gamma H2AX foci 24 h after single or fractionated doses appears to be a useful measure of cellular radiosensitivity that is potentially applicable in the clinic. (c) 2006 Elsevier Ireland Ltd. All rights reserved.