A correlation between residual radiation-induced DNA double-strand breaks in cultured fibroblasts and late radiotherapy reactions in breast cancer patients

Background and purpose: Prediction of late normal tissue reactions to radio therapy would permit tailoring of dosage to each patient. Measurement of re sidual DNA double strand breaks using pulsed field gel electrophoresis (PFG E) shows promise in this field. The aim of this study was to test the predi ctive potential of PFGE in a group of retrospectively studied breast cancer patients. Materials and methods: Thirty nine patients, treated uniformly for breast c ancer 9-15 years previously, with excision of the tumour and radiotherapy t o the breast and drainage areas, were assessed clinically using the LENT SO MA scale, and a 5-mm punch biopsy taken from the buttock. Fibroblast cell s trains were established and used to study residual DNA double strand breaks , using PFGE. Results: There were significant correlations between the DNA assay results and the fibrosis score (r(s) = 0.46; P = 0.003), the combined fibrosis and retraction score (r(s) = 0.45, P = 0.004) and the overall LENT score (r(s) = 0.43; P = 0.006). Using polychotomous logistic regression, the fibroblast DNA assay result was an independent prognostic factor for fibrosis severit y. Conclusions: There is a relationship between residual radiation-induced DNA damage in fibroblasts and the severity of the late normal tissue damage se en in the patients from whom the cells were cultured. (C) 1999 Elsevier Sci ence Ireland Ltd. All rights reserved.