Delayed expression of apoptosis in X-irradiated human leukemic MOLT-4 cells transfected with mutant p53.
Delayed expression of apoptosis in X-irradiated human leukemic MOLT-4 cells transfected with mutant p53.
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DOI：
10.1269/jrr.44.179
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发表时间：
2003-06
影响因子：
2
通讯作者：
H. Nakano;H. Yonekawa;K. Shinohara
中科院分区：
文献类型：
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作者：
H. Nakano;H. Yonekawa;K. Shinohara
在稳定表达突变型P53基因的人白血病MOLT-4细胞(野生型P53)中，用染料排斥试验研究了X射线对细胞存活、凋亡和细胞死亡过程中的长期反应的影响。由集落形成能力确定的细胞存活率以一种表达水平依赖的方式增加，但即使是表达最高的克隆(B3)，这种增加也是部分的。这与先前观察到的B3细胞死亡和凋亡在1.8GyX射线照射后24小时完全被抑制形成鲜明对比。X射线照射后孵育超过24 h的B3细胞的检测显示，B3细胞的死亡和凋亡诱导延迟。Western印迹分析表明，在B3细胞中野生型P53蛋白达到最高水平所需的时间比在MOLT-4中所需的时间更长，并且P53蛋白可能通过Ser-15的磷酸化而稳定下来。这些结果表明，将突变型P53基因导入MOLT-4细胞只是延缓了细胞的凋亡进程，在此期间细胞可以修复X射线所致的损伤，并导致细胞存活率的部分增加。
The effects of X-rays on cell survival, apoptosis, and long-term response in the development of cell death as measured by the dye exclusion test were studied in human leukemic MOLT-4 cells (p53 wild-type) stably transfected with a mutant p53 cDNA expression vector. Cell survival, as determined from colony-forming ability, was increased in an expression level dependent manner, but the increase was partial even with the highest-expressing clone (B3). This contrasts with the prior observation that cell death and apoptosis in B3 are completely inhibited at 24 h after irradiation with 1.8 Gy of X-rays. The examination of B3 cells incubated for longer than 24 h after X-irradiation showed a delay in the induction of cell death and apoptosis. Western blot analysis revealed that the time required to reach the highest level of wild-type p53 protein in B3 was longer than the time in MOLT-4 and that the p53 may be stabilized by the phosphorylation at Ser-15. These results suggest that the introduction of mutant p53 into MOLT-4 merely delays the development of apoptosis, during which the cells could repair the damage induced by X-rays, and results in the partial increase in cell survival.