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Radiation Sensitivity, H2AX Phosphorylation, and Kinetics of Repair of DNA Strand Breaks in Irradiated Cervical Cancer Cell Lines

British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada

Six human cervical cancer cell lines [five human papillomavirus (HPV) positive, one HPV negative] for induction and rejoining of DNA strand breaks and for kinetics of formation and loss of serine 139 phosphorylated histone H2AX (H2AX). X-rays induced the same level of DNA breakage for all cell lines. By 8 hours after 20 Gy, <2% of the initial single-strand breaks remained and no double-strand breaks could be detected. In contrast, 24 hours after irradiation, H2AX representing up to 30% of the initial signal still present. SW756 cells showed almost four times higher background levels of H2AX and no residual H2AX compared with the most radiosensitive HPV-negative C33A cells that showed the lowest background and retained 30% of the maximum level of H2AX. Radiation sensitivity, measured as clonogenic-surviving fraction after 2 Gy, was correlated with the fraction of H2AX remaining 24 hours after irradiation. A substantial correlation with H2AX loss half-time measured over the first 4 hours was seen only when cervical cell lines were included in a larger series of p53-deficient cell lines. Interestingly, p53 wild-type cell lines consistently showed faster H2AX loss half-times than p53-deficient cell lines. We conclude that cell line-dependent differences in loss of H2AX after irradiation are related in part to intrinsic radiosensitivity. The possibility that the presence of H2AX foci may not always signify the presence of a physical break, notably in some tumor cell lines, is also supported by these results.

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