Dose rate effectiveness and potentially lethal damage repair in normal and double-strand break repair deficient murine cells by γ-rays and 5-fluorouracil

SCID (severe combined immunodeficiency) fibroblasts established from C.B17-scid/scid embryos showed higher sensitivity to high (1.105 Gy/min) and low (0.00069 Gy/min) dose rate γ-rays and also to 5-fluorouracil, a cancer sedative producing double-strand breaks, than wildtype cells from C.B17-+/+ embryos. Furthermore, SCID cells were deficient in repairing DNA damage induced by high dose rate γ-rays even after dose fractionation and after 24 h recovery periods, while wildtype cells showed an apparent repair ability on DNA damage after these γ-ray exposures. This is the first report to prove that SCID cells lack the repair of γ-ray-induced potentially lethal damage and also of 5-fluorouracil-induced double-strand breaks. However, SCID cells showed a significantly higher survival rate by low dose rate exposure than by high dose rate exposure as in the case of wildtype cells, indicating that SCID cells have a deficiency in DNA repair for high dose rate γ-rays, but not for low dose rate exposure. This suggests an important finding that the dose rate effect (diminution of cell killing by low dose rate exposure) is caused not only by the repair of double-strand breaks induced by γ-rays but in most parts by less yields of double-strand breaks due to dispersed or low intensity ionization in the cell.