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Mechanisms of Radiation-Induced Apoptosis

辐射诱导细胞凋亡的机制

基本信息

批准号：
02680176
负责人：
OHYAMA Harumi
金额：
$ 1.09万
依托单位：
National Institute of Radiological Sciences (NIRS)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

项目摘要

Thymocytes show typical apoptosis within a few hours following irradiation. Analysis of proteins with two deminsional gel electrophoresis revealed that a few proteins changed associated with the cell death. Inhibitors of protein synthesis and proteinase suppressed the cell death. Threfore, it is supposed that protein synthesis as well as protein degradation playsarole in the development of apoptosis. Ubiquitin gene expression increased slightly in the earlier phase and decreased thereafter in progression of the cell death. Chromatin DNA fragmentation into oligonucteosomal units represents the most characteristic biochemical event in apoptosis. We established microgel electrophoresis technique to detect the DNA cleavage. Results revealed that apoptotic cells showed similar migration pattern with a tear-drop shaped fragmented DNA tail and non-migrating DNA core particle, while viable cells exhibited no DNA migration. The findings indicate that apoptotic breakage of DNA in X-irradiated thymocytes is an "all or none" type event. In the present study, we found several extremely radiosensitive thymic lymphoma cell lines establised in our institute. These cells showed typical apoptosis within a few hours following low doses X-irradiation. Characteristic DNA fragmentation could be detected both by micro and macro get electrophoresis of DNA. Colony forming ability decreased with low doses X-irradiation. Further study on the mechanism of radiation induced apoptosis is now in progress.

胸腺细胞在照射后数小时内表现出典型的凋亡。采用双向凝胶电泳对蛋白质进行分析，发现一些蛋白质发生了变化，与细胞死亡相关。蛋白质合成抑制剂和蛋白酶抑制剂抑制细胞死亡。因此，认为蛋白质的合成和降解在细胞凋亡的发生发展中起着重要作用。泛素基因表达在细胞死亡的早期阶段略有增加，此后随着细胞死亡的进展而降低。染色质DNA断裂成寡核小体单位代表了细胞凋亡中最具特征的生化事件。建立了微凝胶电泳技术检测DNA断裂。结果显示，凋亡细胞表现出类似的迁移模式，具有泪滴状的片段化DNA尾部和非迁移的DNA核心颗粒，而活细胞则没有表现出DNA迁移。研究结果表明，在X射线照射胸腺细胞的DNA凋亡断裂是一个“全部或没有”类型的事件。在本研究中，我们发现了几个非常放射敏感的胸腺淋巴瘤细胞系在我们的研究所建立。这些细胞在低剂量X射线照射后数小时内表现出典型的凋亡。DNA的显微电泳和宏观电泳均能检测到特征性的DNA断裂。低剂量X射线照射后，细胞集落形成能力下降。辐射诱导细胞凋亡的机制正在进一步研究中。