Beamish H, Khanna K K, Lavin M F
Queensland Cancer Fund Research Unit, Queensland Institute of Medical Research, Bancroft Centre, Brisbane, Australia.
Radiat Res. 1994 Apr;138(1 Suppl):S130-3.
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.
哺乳动物细胞暴露于电离辐射会导致在细胞周期的多个不同检查点处正常进程延迟。辐射后共济失调毛细血管扩张症细胞的这些检查点异常已有描述。在本报告中，我们表明这些异常发生在几种共济失调毛细血管扩张症淋巴母细胞系细胞周期的不同阶段。用含羞草碱或阿非迪霉素使共济失调毛细血管扩张症细胞在G1期晚期同步化并暴露于辐射后，与受辐射的对照细胞相比，进入S期的延迟减少。共济失调毛细血管扩张症细胞未能表现出G1期延迟，同时辐射激活肿瘤抑制基因p53产物（一种参与G1/S期延迟的蛋白质）的能力降低。当追踪受辐射的G1期细胞进入随后的G2期和G1期时，共济失调毛细血管扩张症细胞在G2期的积累比对照细胞更明显。当细胞在S期受到辐射时，延迟程度在G2期更明显，共济失调毛细血管扩张症细胞延迟程度更大。这些结果表明，G1期和S期均缺乏初始延迟导致了该综合征中观察到的放射敏感性。
