Lack of correlation between residual radiation-induced DNA damage, in keratinocytes assayed directly from skin, and late radiotherapy reactions in breast cancer patients

Purpose: To study the relationship between the severity of late reactions t o radiotherapy in breast cancer patients, and the extent of residual radiat ion-induced DNA damage, using a rapid assay of keratinocytes obtained direc tly from skin biopsies. Methods and Materials: A review was made of 32 patients with breast cancer, treated uniformly by radiotherapy between 1983 and 1988, following breast- conserving surgery. Their late radiotherapy reactions were scored (9-14 yea rs post-radiotherapy) using a modified LENT SOMA scale, and a 5-mm buttock skin punch biopsy was obtained. Intact skin was irradiated at room temperat ure, and after allowing 24 h for repair, the tissue was disaggregated and t he cells processed for pulsed field gel electrophoresis (PFGE). Residual DN A damage was expressed as the fraction of DNA released (FDR) following 150 Gy. Results: Studies using flow cytometry on disaggregated breast skin showed t hat over 90% of the cells were keratinocytes. The PFGE assay was robust wit h low background FDRs in unirradiated skin samples (mean 3.2%) and a wide r ange of FDRs following irradiation from 11.5% to 26.6%. No correlation was found between the FDR at 150 Gy (FDR 150) and any of the late reaction scor es or retrospective acute reaction scores. There was, however, a borderline significant correlation for family history and FDR 150 (p = 0.059). Conclusion: Rapid measurement of residual DNA damage in irradiated differen tiated keratinocytes, the predominant cell population in skin biopsies, sho wed no correlation with the severity of symptomatic early or documented lat e reactions in a retrospectively studied group of 32 breast cancer patients . (C) 1999 Elsevier Science Inc.