ZHOU Ping-kun,SUI Jian-li,WU De-chang.Study on spindle-damaging induced apoptosis in malignantly transformed cells generated by α-particles[J].Chinese Journal of Radiological Medicine and Protection,2005,25(1):6-8 |
Study on spindle-damaging induced apoptosis in malignantly transformed cells generated by α-particles |
Received:July 05, 2004 |
DOI: |
KeyWords:particles Carcinogenesis Spindle Apoptosis |
FundProject: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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Abstract:: |
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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