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1: Radiother Oncol. 2006 Aug;80(2):223-9. Epub 2006 Aug 14.
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Phosphorylated histone H2AX in relation to cell survival in tumor cells and xenografts exposed to single and fractionated doses of X-rays.

Klokov D, MacPhail SM, Banáth JP, Byrne JP, Olive PL.

Medical Biophysics Department, British Columbia Cancer Research Centre, Vancouver, BC, Canada.

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 gammaH2AX 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 anti-gammaH2AX antibodies for analysis by flow and image cytometry. The relative amount of residual gammaH2AX and the percentage of cells with <3 foci were compared with the clonogenic surviving fraction measured for the same population. RESULTS: The fraction of gammaH2AX remaining 24h after X-irradiation relative to peak levels 1h after exposure was correlated with radiosensitivity (SF2) for 18 human tumor cell lines. The fraction of SiHa, C33A and WiDr cells with <3 gammaH2AX 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 gammaH2AX foci 24h after single or fractionated doses appears to be a useful measure of cellular radiosensitivity that is potentially applicable in the clinic.

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PMID: 16905207 [PubMed - indexed for MEDLINE]