Abstract
Epstein–Barr virus-immortalized lymphoblastoid cell lines were derived from five patients with late radionecrosis. Two of these cell lines exhibited postradiation viability levels intermediate between normal cell lines and that from an individual with ataxia telangiectasia. Compared with controls, these two cell lines exhibited impaired ability to rejoin DNA double-strand breaks on pulsed-field gel electrophoresis and 6–10-fold reduced DNA-dependent protein kinase (DNA-PK) activity in vitro in cell-free extracts. Immunoblotting showed normal levels of Ku70, Ku80 and XRCC4 and the presence of DNA-PKcs in both cell lines. These findings suggest that DNA-PK might be an important factor affecting the predisposition of radiotherapy patients to late radionecrosis.
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Acknowledgements
Our thanks to Professor Trevor McMillan and colleagues in Professor Malcolm Dunlop's group for discussion and advice, and to Professor Malcolm Paterson for a critical reading of the manuscript. This work was supported by grants from the Singapore National Cancer Centre, Singapore Cancer Society, the Singapore National Medical and SingHealth Research Councils, the Melville Trust for the Care and Cure of Cancer and the Scottish Hospitals Endowments Research Trust.
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Loong, S., Korzh, S. & Price, A. Reduced DNA-dependent protein kinase activity in two cell lines derived from adult cancer patients with late radionecrosis. Oncogene 23, 5562–5566 (2004). https://doi.org/10.1038/sj.onc.1207771
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DOI: https://doi.org/10.1038/sj.onc.1207771