title: Ionizing radiation and cell cycle progression in ataxia telangiectasia.
abstract: 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 G1 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 G1-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 G1/S-phase delay. When the progress of irradiated G1-phase cells was followed into the subsequent G2 and G1 phases ataxia telangiectasia cells showed a more pronounced accumulation in G2 phase than control cells. When cells were irradiated in S phase the extent of delay was more evident in G2 phase and ataxia telangiectasia cells were delayed to a greater extent. These results suggest that the lack of initial delay in both G1 and S phases contributes to the radiosensitivity observed in this syndrome.
authors.affiliation: Queensland Cancer Fund Research Unit, Queensland Institute of Medical Research, Bancroft Centre, Brisbane, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Beamish
authors.forename: K K
authors.initials: KK
authors.lastname: Khanna
authors.forename: M F
authors.initials: MF
authors.lastname: Lavin
mesh_terms: D001260:Ataxia Telangiectasia / Q000473:pathology*; D002453:Cell Cycle / Q000528:radiation effects*; D002461:Cell Line, Transformed; D015870:Gene Expression / Q000528:radiation effects; D016158:Genes, p53; D006801:Humans; D011839:Radiation, Ionizing; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53