A CORRELATION BETWEEN RESIDUAL DNA DOUBLE-STRAND BREAKS AND CLONOGENIC MEASUREMENTS OF RADIOSENSITIVITY IN FIBROBLASTS FROM PRERADIOTHERAPYCERVIX CANCER-PATIENTS

Purpose: To study the relationship between residual DNA damage and clo nogenic measurements of radiosensitivity in fibroblasts from pretreatm ent cervix cancer patients. Methods and Materials: Early passage vagin al fibroblasts from nine preradiotherapy cervix cancer patients and tw o radiosensitive skin fibroblast cell strains were studied. Cell survi val was measured by clonogenic assay following both high and low dose rate irradiation. Residual DNA damage was measured using pulsed-field gel electrophoresis (PFGE) after irradiating radiolabeled, plateau-pha se cells at 37 degrees C and allowing 24 h for repair. DNA damage was expressed both in terms of the residual damage slope (fitted to data f rom 60 to 150 Gy) and the fraction of activity released (FAR) followin g 150 Gy. Results: The surviving fraction at 2 Gy (SF2) values after h igh dose rate irradiation for the vaginal fibroblasts ranged from 0.15 to 0.32 (a 2.2-fold difference). When the two radiosensitive cell str ains were included, residual damage, expressed as the residual damage slope, correlated with alpha (r = 0.82, p = 0.002), D bar (r = -0.91, p < 0.001) and SF2 (p = -0.79, p = 0.004), and when the vaginal fibrob lasts alone were studied, the residual damage slope again correlated w ith clonogenic survival, although less strongly [alpha (r = 0.66,p = 0 .053), D bar (r = -0.83, p = 0.006), and SF2 (r = -0.63, p = 0.07)]. W ithin the group of vaginal fibroblasts there was a 4.0-fold difference in residual DNA damage slope. When residual damage was expressed as F AR at 150Gy, then for all cell strains the correlations were alpha: r = 0.78, p = 0.004, D bar: r = -0.86, p = 0.001, and SF2: r = -0.78, p = 0.004, and for the vaginal fibroblast strains alone the correlations were alpha: r = 0.60, p = 0.088, D bar: r = -0.75, p = 0.02, and SF2: r = 0.62, p = 0.077. Conclusion: This study confirms previous finding s that residual DNA damage correlates with clonogenic survival in fibr oblasts. In addition, it demonstrates a correlation for fibroblasts fr om pretreatment cervix cancer patients demonstrating a relatively smal l range of SF2 values. (C) 1997 Elsevier Science Inc.