IONIZING-RADIATION AND CELL-CYCLE PROGRESSION IN ATAXIA-TELANGIECTASIA

Exposure of mammalian cells to ionizing radiation causes delay in normal progress through the cell cycle at a number of different checkpoints. Abnormalities in these checkpoints have been described for ataxia telangiectasia cells after irradiation. In this report we show that these abnormalities occur at different phases in the cell cycle in several ataxia telangiectasia lymphoblastoid cells. Ataxia telangiectasia cells, synchronized in late G(1) phase with either mimosine or aphidicolin and exposed to radiation, showed a reduced delay in entering S phase compared to irradiated control cells. Failure to exhibit G(1)-phase delay in ataxia telangiectasia cells is accompanied by a reduced ability of radiation to activate the product of the tumor suppressor gene p53, a protein involved in G(1)/S-phase delay. When the progress of irradiated G(1)-phase cells was followed into the subsequent G(2) and G(1) phases ataxia telangiectasia cells showed a more pronounced accumulation in G(2) phase than control cells. When cells were irradiated in S phase the extent of delay was more evident in G(2) phase and ataxia telangiectasia cells were delayed to a greater extent. These results suggest that the lack of initial delay in both G(1) and S phases contributes to the radiosensitivity observed in this syndrome.