Reduced DNA-dependent protein kinase activity in two cell lines derived from adult cancer patients with late radionecrosis.
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.
Loong
Susan L E
SL
Division of Oncology, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland, UK.
Korzh
Svitlana
S
Price
Allan
A
D004247:DNA / Q000378:metabolism* / Q000528:radiation effects; D004260:DNA Repair / Q000502:physiology* / Q000528:radiation effects; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D009369:Neoplasms / Q000532:radiotherapy*; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000528:radiation effects
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D004247:DNA; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases