THE RADIOSENSITIVITY OF HUMAN FIBROBLAST CELL-LINES CORRELATES WITH RESIDUAL LEVELS OF DNA DOUBLE-STRAND BREAKS

Purpose: To study the correlation of residual DNA double-strand breaka ge after irradiation and cellular radiosensitivity in cells showing ma rked differences in radiosensitivity. Materials nod methods: The level s of DNA double-strand breaks remaining at 4 h after irradiation were measured by graded-voltage gel electrophoresis in fibroblast cell stra ins derived from seven individuals either with normal radiosensitivity (n = 2), or with genetic abnormalities known to show increased (two a taxia telangiectasia, one scid) or possibly decreased (two Li-Fraumeni family members) sensitivity. Results: The slope of the dose-response curve for DNA breaks remaining unrepaired at 4 h showed a highly signi ficant correlation with cellular radiosensitivity characterized by SF2 , alpha, or (D) over bar (r greater than or equal to 0.91, P < 0.001). Hence, this measure of genotoxic damage was predictive of radiation s ensitivity for cells affected by a variety of mutations in different d amage singalling/repair components. Discussion: This correlation confi rms another published study and extends it to cell lines with other ge netic defects. The technique may be useful in the development of rapid assays to predict the sensitivity of normal tissues in patients recei ving radiotherapy. (C) 1997 Elsevier Science Ireland Ltd. All rights r eserved.