DOSE-RATE EFFECTIVENESS AND POTENTIALLY LETHAL DAMAGE REPAIR IN NORMAL AND DOUBLE-STRAND BREAK REPAIR-DEFICIENT MURINE CELLS BY GAMMA-RAYS AND 5-FLOUROURACIL

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 gamma-rays and also to 5-fluorour acil, a cancer sedative producing double-strand breaks, than wildtype cells from C.B17-+/+ embryos. Furthermore, SCID cells were deficient i n repairing DNA damage induced by high dose rate gamma-rays even after dose fractionation and after 24 h recovery periods, while wildtype ce lls showed an apparent repair ability on DNA damage after these gamma- ray exposures. This is the first report to prove that SCID cells lack the repair of gamma-ray-induced potentially lethal damage and also of 5-fluorouracil-induced double-strand breaks. However, SCID cells showe d a significantly higher survival rate by low dose rate exposure than by high dose rate exposure as in the case of wildtype cells, indicatin g that SCID cells have a deficiency in DNA repair for high dose rate g amma-rays, but not for low dose rate exposure. This suggests an import ant finding that the dose rate effect (diminution of cell killing by l ow dose rate exposure) is caused not only by the repair of double-stra nd breaks induced by gamma-rays but in most parts by less yields of do uble-strand breaks due to dispersed or low intensity ionization in the cell. (C) 1998 Elsevier Science Ireland Ltd.