DOSE-RATE EFFECT ON INDUCTION AND REPAIR RATE OF RADIATION-INDUCED DNA DOUBLE-STRAND BREAKS IN A NORMAL AND AN ATAXIA-TELANGIECTASIA HUMAN FIBROBLAST CELL-LINE

Using pulsed-field gel electrophoresis (PGFE), we measured DNA double- strand breaks (DSB) in a normal human fibroblast and in a cell line de rived from a patient suffering from ataxia telangiectasia (AT), a synd rome associated with a hypersensitivity to ionizing radiation. Initial DSB levels assessed after irradiation at 4 degrees C are similar in b oth cell lines. The DSB repair rate was measured after 30 Gy delivered at 4 degrees C and followed by an incubation at 37 degrees C for 24 h . In AT cells, the DSB repair rate is faster between 0.5 and 9 h and s lower between 9 and 24 h. In addition, the DSB levels were measured af ter irradiation at 37 degrees C at 0.01 Gy min(-1) (5-40 Gy). The shap e of the curves was curvilinear and a plateau was reached at 10 Gy in the control. After an irradiation at 37 degrees C, DSB levels were sig nificantly higher in AT cells than in the normal fibroblast cells. A m odel was developed assuming that DSB induction is independent of tempe rature and that DSB repair rate is independent of dose-rate and dose. This model was used to predict the 37 degrees C DSB data on the basis of the 4 degrees C data. Experimental data and predictions are in agre ement, thus validating the above assumptions. It is suggested that, ev en for extreme situations such as 30 Gy delivered at 4 degrees C or 30 Gy delivered at 37 degrees C at 0.01 Gy min(-1), DSB induction and re pair are identical. Our results could be interpreted assuming an heter ogeneity of DSB. A small fraction of DSB is slowly repaired. This frac tion is lower in control than in AT cells. By protracting repair time, the 37 degrees C low-dose rate experiments permit a cleaner distincti on between AT and control cells.