Selective elimination of human lymphoid cells with unstable chromosome aberrations by p53-dependent apoptosis.
Selective elimination of human lymphoid cells with unstable chromosome aberrations by p53-dependent apoptosis.
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通过 p53 依赖性细胞凋亡选择性消除具有不稳定染色体畸变的人淋巴细胞。
DOI：
10.1093/carcin/18.1.201
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发表时间：
1997
期刊：
影响因子：
4.7
通讯作者：
Jordan,R
中科院分区：
文献类型：
--
作者：
Schwartz,JL;Jordan,R
p53表达的改变与基因组不稳定有关，可能是因为p53的缺失导致无法通过凋亡或诱导细胞周期阻断来消除受损的、因此可能不稳定的细胞。我们通过检测凋亡对两种等基因人b淋巴母细胞样细胞系x射线诱导的染色体畸变频率的影响来验证这一假设；对诱导凋亡敏感的TK6和对诱导凋亡有抗性的p53突变体WI-L2-NS。虽然TK6对x射线的细胞毒性作用比WI-L2-NS细胞更敏感，但其诱导的染色体畸变较少。phorbol 12-肉豆蔻酸酯13-乙酸酯（PMA）对TK6细胞凋亡的抑制作用导致x射线诱导的畸变频率与WI-L2-NS相似。结果支持了细胞凋亡选择性清除受损细胞的假设。与细胞凋亡相关的畸变频率降低主要见于不稳定类型的畸变；无中心染色体片段和双中心染色体。对诱导平衡易位的频率没有影响，平衡易位是双中心的稳定对应物。不能去除具有不稳定畸变类型的细胞与伴随p53活性丧失的基因组不稳定相一致。
Alterations in p53 expression are associated with genomic instability, presumably because loss of p53 leads to an inability to eliminate damaged and therefore potentially unstable cells by apoptosis or by induced cell cycle block. We tested this hypothesis by examining the influence of apoptosis on X-ray-induced chromosome aberration frequency in two isogenic human B-lymphoblastoid cell lines; TK6, which is sensitive to the induction of apoptosis, and WI-L2-NS, a p53 mutant resistant to apoptosis induction. While TK6 was more sensitive than WI-L2-NS cells to the cytotoxic effects of X-rays, it showed fewer induced chromosome aberrations. Inhibition of apoptosis in TK6 cells with phorbol 12-myristate 13-acetate (PMA) resulted in X-ray-induced aberration frequencies similar in magnitude to WI-L2-NS. The results support the hypothesis that apoptosis acts to selectively remove damaged cells. The reduction in aberration frequency associated with apoptosis was seen primarily for unstable types of aberrations; acentric chromosome fragments and dicentric chromosomes. There was no effect on the induced frequency of balanced translocations, the stable counterpart to dicentrics. The failure to remove cells with unstable types of aberrations is consistent with the genomic instability that accompanies loss of p53 activity.
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影响因子：
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影响因子：
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