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

Abstract

Using pulsed-field gel electrophoresis (PGFE) we measured DNA double-strand breaks (DSB) in a normal human fibroblast and in a cell derived from a patient suffering from ataxia telangiectasia (AT), a syndrome associated with a hypersensitivity to ionizing radiation. Initial DSB levels assessed after irradiation at 4°C are similar in both cell lines. The DSB repair rate was measured after 30 Gy delivered at 4°C and followed by an incubation at 37°C for 24 h. In AT cells, the DSB repair rate is faster between 0.5 and 9 h and slower between 9 and 24 h. In addition, the DSB levels were measured after irradiation at 37°C at 0.01 Gy min −1 (5–40 Gy). The shape of the curves was curvilinear and a plateau was reached at 10 Gy in the control. After an irradiation at 37°C, DSB levels were significantly higher in AT cells than in the normal fibroblast cells. A model was developed assuming that DSB induction is independent of temperature and that DSB repair rate is independent of dose-rate and dose. This model was used to predict the 37°C DSB data on the basis of the 4°C data. Experimental data and predictions are in agreement, thus validating the above assumptions. It is suggested that, even for extreme situations such as 30 Gy delivered at 4°C or 30 Gy delivered at 37°C at 0.01 Gy min −1 DSB induction and repair are identical. Our results could be interpreted assuming an heterogeneity of DSB. A small fraction of DSB is slowy repaired. This fraction is lower in control than in AT cells. By protracting repair time, the 37°C low-dose rate experiments permit a cleaner distinction between AT and control cells.