Radiation-induced apoptosis in sensitive and resistant cells isolated from a mouse lymphoma.
Radiation-induced apoptosis in sensitive and resistant cells isolated from a mouse lymphoma.
复制标题
DOI：
--
复制
发表时间：
1994-12
影响因子：
2.6
通讯作者：
Michael D. Story;David Voehringer;C. Malone;M. Hobbs;Ray Meyn
中科院分区：
文献类型：
--
作者：
Michael D. Story;David Voehringer;C. Malone;M. Hobbs;Ray Meyn
从小鼠淋巴瘤（LY-TH）中分离细胞并在体外生长。它们在低剂量照射后1 h出现核酸内切片段化DNA，对辐射诱导的细胞凋亡敏感。在接受5戈伊照射后4小时，80%的DNA被核酸内切酶切割。DNA双链断裂（dsb）的形成诱导细胞凋亡比单链断裂（ssb）的形成诱导更有效。长期培养后，LY-TH培养物变得难以凋亡。凋亡允许细胞（LY-作为，从LY-TH细胞克隆）比克隆扩增的凋亡难治细胞（LY-ar）的放射敏感性高3倍。低剂量率照射和照射后25 ℃维持5小时，LY-ar细胞而不是LY-as细胞中没有损伤，表明LY-as细胞中存在修复缺陷。dsb重接动力学分析显示dsb重接的初始阶段没有差异。然而，1小时后，相对dsb的LY-作为变体增加的内切核酸裂解开始。辐射诱导的细胞凋亡的信号在LY-作为细胞是独立的DNA双链断裂修复途径，并出现确定的初始事件，而在LY-ar细胞，因为在细胞凋亡途径的抑制，生存增强和修改的修复过程。
Cells were isolated from a mouse lymphoma (LY-TH) and grown in vitro. They were susceptible to radiation-induced apoptosis after low doses with the appearance of endonucleolytically fragmented DNA 1 h after irradiation. Four hours after receiving 5 Gy, 80% of the DNA was endonucleolytically cleaved. Apoptosis induction by DNA double-strand break (dsb) formation was more effective compared with induction by single-strand break (ssb) formation. After long-term culturing, LY-TH cultures became refractory to apoptosis. Apoptosis-permissive cells (LY-as, cloned from LY-TH cells) were three times more radiosensitive than clonally expanded apoptosis-refractory cells (LY-ar). Low dose-rate irradiation and maintenance at 25 degrees C for 5 h postirradiation was sparing in LY-ar but not LY-as cells, suggesting a repair deficiency in LY-as cells. Analysis of dsb rejoining kinetics revealed no difference in the initial phase of dsb rejoining. After 1 h, however, relative dsbs in the LY-as variant increased as endonucleolytic cleavage was initiated. Signalling for radiation-induced apoptosis in LY-as cells was independent of the DNA dsb repair pathway and appeared determined by initial events, whereas in LY-ar cells, because of an inhibition in the apoptotic pathway, survival was enhanced and modifiable by repair processes.