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.
中科院分区:
文献类型:
--
作者:
Klokov, Dmitry;MacPhail, Susan M.;Olive, Peggy L.
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.