27. Dose Rate Effects on Cell Killing by -irradiation in Ataxia Telangiectasia Lymphoblastoid Cells

Ikuko Furuno-Fukushi and Kouichi Tatsumi

Keywords: ataxia telangiectasia, dose rate effect, double-strand break repair

To investigate the dependency of dose rate effect on ATM gene, loss of the clonogenicity of lymphoblastoid cells derived from a patient with ataxia telangiectasia (AT1-1) was studied after exposure to -rays at dose rates of 30 Gy/h, 0.21 Gy/h and 0.0048 Gy/h. AT1-1 cells were very sensitive to killing by high dose rate -rays, and showed a comparable sensitivity to those for scid (XRCC7) and LX830 (XRCC4) cells. Survival curves showed an increase in D₀ when AT1-1 cells were irradiated at the lower dose rates as compared to the high dose rate. Split-dose experiments for -rays of 30 Gy/h were also carried out in AT1-1 cells. When results for two 0.5 Gy doses, separated by a variable interval, were compared with those of a single dose of 1 Gy, dividing the dose into two fractions was seen to have little effect on cell survival. It was determined that scid and LX830 cells were defective in the repair of DNA double-strand breaks (DSBs) and that the two cell lines failed to show the dose rate effect of -rays. Radiation hypersensitivity in AT cells has been believed to result from cell-cycle checkpoint defects, especially since no substantial defect in the capacity to rejoin DNA DSBs has been successfully detected for AT cells following irradiation. Hence, it was suggested that the dose rate effect on cell killing by -rays was strongly associated with the efficient repair processes of DNA DSBs.