DOSE-RATE EFFECT ON RADIATION-INDUCED DNA DOUBLE-STRAND BREAKS IN THEHUMAN FIBROBLAST HF19 CELL-LINE

We measured DNA double-strand breaks (dsbs) immediately after exposure of a non-transformed human fibroblast cell line (HF19) to gamma-rays (0-40 Gy) at four dose-rates (10, 1, 0.1, and 0.01 Gy.min(-1)) at 37 d egrees C using clamped homogeneous electric field (CHEF) gel electroph oresis. The shape of the dose-response curves, which could be approxim ated by a straight line over the range 0-20 Gy for irradiation at 4 de grees C, became curvilinear when irradiation was carried out at 37 deg rees C at 10, 1, 0.1, and 0.01 Gy.min(-1) and reached a plateau at 10 Gy after irradiation at 0.01 Gy.min(-1). We present a mathematical ana lysis that predicts the results of irradiation at 37 degrees C from ds b induction and repair data obtained at 4 degrees C, followed by incub ation for repair at 37 degrees C. The model assumes that the rate of d sb rejoining changes continuously with repair time and that it is inde pendent of dose and dose-rate in the range 10-40 Gy. The model also as sumes a linear induction of dsb with dose at 4 degrees C and dsb induc tion is independent of dose-rate and of temperature during irradiation . Independent measurements of dsb induction at 4 degrees C and of repa ir rate accurately predict the dsb levels after irradiation at 37 degr ees C, during which both phenomena occur simultaneously.