Strasser-Wozak E M, Hartmann B L, Geley S, Sgonc R, Böck G, Hattmannstorfer R, Wolf H, Pavelka M, Kofler R
Institute for General and Experimental Pathology, Division of Molecular Pathophysiology, University of Innsbruck Medical School, A-6020, Innsbruck, Austria.
Cell Death Differ. 1998 Aug;5(8):687-93. doi: 10.1038/sj.cdd.4400402.
The tumor suppressor p53 has been implicated in gamma irradiation-induced apoptosis. To investigate possible consequences of wild-type p53 loss in leukemia, we studied the effect of a single dose of gamma irradiation upon p53-deficient human T-ALL (acute lymphoblastic leukemia) CCRF - CEM cells. Exposure to 3 - 96 Gy caused p53-independent cell death in a dose and time-dependent fashion. By electron microscopic and other criteria, this cell death was classified as apoptosis. At low to intermediate levels of irradiation, apoptosis was preceded by accumulation of cells in the G2/M phase of the cell division cycle. Expression of Bcl-2 and Bax were not detectably altered after irradiation. Expression of the temperature sensitive mouse p53 V135 mutant induced apoptosis on its own but only slightly increased the sensitivity of CCRF - CEM cells to gamma irradiation. Thus, in these, and perhaps other leukemia cells, a p53- and Bcl-2/Bax-independent mechanism is operative that efficiently senses irradiation effects and translates this signal into arrest in the G2/M phase of the cell cycle and subsequent apoptosis.
肿瘤抑制因子p53与γ射线诱导的细胞凋亡有关。为了研究野生型p53缺失在白血病中的可能后果，我们研究了单剂量γ射线对p53缺陷型人T-ALL（急性淋巴细胞白血病）CCRF - CEM细胞的影响。暴露于3 - 96 Gy会以剂量和时间依赖的方式导致p53非依赖性细胞死亡。通过电子显微镜和其他标准，这种细胞死亡被归类为凋亡。在低至中等水平的照射下，细胞凋亡之前细胞在细胞分裂周期的G2/M期积累。照射后Bcl-2和Bax的表达没有明显改变。温度敏感型小鼠p53 V135突变体的表达自身可诱导细胞凋亡，但仅略微增加CCRF - CEM细胞对γ射线的敏感性。因此，在这些以及可能的其他白血病细胞中，一种不依赖p53和Bcl-2/Bax的机制起作用，该机制能有效地感知照射效应并将此信号转化为细胞周期G2/M期的阻滞及随后的凋亡。
