| 周平坤,隋建丽,吴德昌.α粒子诱发癌变细胞的纺锤体损伤凋亡机理研究[J].中华放射医学与防护杂志,2005,25(1):6-8 |
| α粒子诱发癌变细胞的纺锤体损伤凋亡机理研究 |
| Study on spindle-damaging induced apoptosis in malignantly transformed cells generated by α-particles |
| 投稿时间：2004-07-05 |
| DOI： |
| 中文关键词: α粒子 细胞癌变 纺锤体 凋亡 |
| 英文关键词:particles Carcinogenesis Spindle Apoptosis |
| 基金项目:国家自然科学基金资助项目(30270423);军队医学杰出中青年基金资助项目(01J006) |
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| 摘要点击次数: 2462 |
| 全文下载次数: 2002 |
| 中文摘要: |
| 目的 从纺锤体损伤诱导的凋亡反应,探讨α粒子诱发癌变细胞的遗传不稳定性机理。方法 用噻氨酯哒唑破坏纺锤体微管蛋白诱发细胞凋亡,Giemsa染色以及3种荧光染料(FDA、Hoechster33258和PI)复合染色检测凋亡;松胞素B阻止细胞分裂,分析凋亡与细胞周期时相的关系。结果 0.3μgml噻氨酯哒唑作用6～48h,癌变细胞BERP35T1和BERP35T4的凋亡发生率要显著低于正常BEP2D细胞2～25倍(P<0.01),而且正常细胞的凋亡主要是发生在细胞有丝分裂前,癌变细胞特别是BERP35T4细胞,有近50%的凋亡是发生在有丝分裂之后。结论 纺锤体损伤后凋亡机理异常,将导致非整倍体或多倍体的子代细胞增多,加剧α粒子照射细胞的遗传不稳定性。 |
| 英文摘要: |
| Objective To investigate the mechanism of cytogenetic instability in α-particles-transformed cells through the analysis of spindle-damaging induced apoptosis. Methods The cells were treated with 0.3 μg/ml of nocodazole, a microtubule-disrupting agent, to induce apoptosis. Apoptotic cells were detected by combined fluorescence staining assay (FDA, Hoechster33258 and PI) as well as apoptotic morphological analysis of Giemsa-stained cells. Cytochalasin B was used to block cell division for identifying the apoptotic cells taking place either before or after mitotic division. Results The extent of apoptosis induced by nocodazole was significantly lower (2-2.5 fold, P<0.01) in two transformed cell lines, BERP35T1 and BERP35T4, than that in their parental BEP2D cells. The induced apoptosis was found to take place dominantly before mitotic division in BEP2D cells. In BERP35T4 cells, however, one half of induced apoptosis occurred before mitotic division and another half occurred after division in binucleated cells when co-treated with cytochalasin B. This result indicated that a prompt apoptotic mechanism was triggered by microtubule disruption or spindle failure in BEP2D cells. In contrast, BERP35T4 cells could escape the mitotic arrest and apoptosis induced by nocodazole, and followed by their adaptation and mitotic restitution, some of them survived and consequently converted into cells with genomic instability. Conclusion The abnormal responsiveness of spindle-damaging induced apoptosis could result in the increase of aneuploid or polyploid cells. These aberrant cells might contribute to the increased tendency for the malignant transformation of α-particles-irradiated cells. |
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