The radiosensitivity of human fibroblast cell lines correlates with residual levels of DNA double-strand breaks.

Abstract

PURPOSE: To study the correlation of residual DNA double-strand breakage after irradiation and cellular radiosensitivity in cells showing marked differences in radiosensitivity. MATERIALS AND METHODS: The levels of DNA double-strand breaks remaining at 4 h after irradiation were measured by graded-voltage gel electrophoresis in fibroblast cell strains derived from seven individuals either with normal radiosensitivity (n = 2), or with genetic abnormalities known to show increased (two ataxia 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 significant correlation with cellular radiosensitivity characterized by SF2, alpha, or D (r > or = 0.91, P < 0.001). Hence, this measure of genotoxic damage was predictive of radiation sensitivity for cells affected by a variety of mutations in different damage signalling/repair components. DISCUSSION: This correlation confirms another published study and extends it to cell lines with other genetic defects. The technique may be useful in the development of rapid assays to predict the sensitivity of normal tissues in patients receiving radiotherapy.