Perturbations of cell-cycle progression in gamma-irradiated ataxia telangiectasia and Huntington's disease cells detected by DNA flow cytometric analysis.
The effects of ionizing radiation on cell-cycle progression in lymphoblastoid cell lines derived from ataxia telangiectasia (AT) and Huntington's disease (HD) patients, and from normal individuals, were studied using DNA flow cytometric analysis. A dose of 100 rad gamma irradiation blocked a proportion of normal and HD cells in G1. A higher radiation dose applied to normal cells increased the number of cells blocked in G1 and significantly delayed cells which were in S at the time of irradiation from reaching G2 DNA content. The reduced cumulative mitotic index in irradiated cultures of normal cells 2 h after irradiation suggests that cells in G2 at the time of irradiation are delayed before entering mitosis. After irradiation HD cells responded similarly to normal cells except that a greater proportion of HD cells were blocked in G1. AT cells do not show the normal delay in progression from G1 to S, or from S to G2 in the first cycle after irradiation. The cumulative mitotic index was reduced in irradiated cells, implying that they are delayed in G2. Thus AT cells did not recognize or respond to signals from damaged DNA which in normal and HD cells caused a proportional block in G1 and an S-phase delay. The only point of arrest in cell-cycle progression in irradiated AT cells was in G2.
D001260:Ataxia Telangiectasia / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D005434:Flow Cytometry; D005720:Gamma Rays; D006801:Humans; D006816:Huntington Disease / Q000473:pathology*; D007399:Interphase / Q000187:drug effects