The effects of ionizing radiation on cell cycle progression in ataxia telangiectasia.
Although ataxia telangiectasia (AT) cells are more sensitive than normal cells to killing by ionizing radiation, their DNA synthesis is more resistant to inhibition by radiation. It was thought that this anomaly in DNA synthesis was likely to perturb cell cycle progression. Flow cytometry and the fraction of labelled mitoses (FLM) were used to investigate effects of irradiation in normal and AT cell lines. The FLM indicated that radiation apparently induced a longer G2 delay in normal cells than in AT cells. However, flow cytometry showed that radiation induced much larger and more prolonged increases in the proportion of G2 cells in AT than in normals. AT populations also showed much larger postirradiation decreases in viable cell numbers. These data suggest that a large proportion of the radiosensitive AT cells are not reversibly blocked in G2 but die there, and never proceed through mitosis. The less radiosensitive normal cells are delayed in G2 and then proceed through mitosis. We suggest that the apparently shorter radiation-induced mitotic delay seen in AT cells by FLM is not real but is an artifact arising from perturbation of steady state conditions by selective elimination of a particular cohort of AT cells. Accumulation of AT cells in G2 is compatible with radiosensitivity of these cells and may arise from a defect in DNA repair or an anomaly in DNA replication.
D001260:Ataxia Telangiectasia / Q000503:physiopathology*; D002453:Cell Cycle / Q000528:radiation effects*; D002460:Cell Line; D004261:DNA Replication / Q000528:radiation effects*; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000528:radiation effects; D008938:Mitosis / Q000187:drug effects; D008940:Mitotic Index / Q000528:radiation effects