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Study on abnormality of DNA recombination in LEC strain rat

LEC品系大鼠DNA重组异常的研究

基本信息

批准号：
07660409
负责人：
HAYASHI Masanobu
金额：
$ 1.34万
依托单位：
Rakuno Gakuen University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07660409/
关键词：
LEC rat DNA recombination Radiation hypersensitivity Drug-sensitivity Deficiency in G1 arrest Repair of DNA double strand breaks Cell cycle Radioresistant DNA synthesis ブレオマイシン DNA組み換え株化細胞

项目摘要

1. Immortalized cell lines from LEC strain (LEC) rats by SV40 large T antigen were more sensitive to X-irradiation than the cell lines from WKAH strain (WKAH) rats, but not to UV-irradiation.2. DNA synthesis in the cell lines of LEC rats was more resistant to X- and UV-irradiation than that of WKAH rats.3. The radiation-induced delay in the progression from the G1 phase to S phase (G1 arrest) was observed in WKAH cells, but not in LEC cells. The intensities of the p53 protein bands increased following irradiation in WKAH cells, but not in LEC cells.4. LEC rat cells were 2-to 3-fold more sensitive to bleomycin (BLM) that induces DNA double-strand breaks (dsbs), and to cross-linking agent, mitomycin C,than WKAH rat cells, while they were slightly sensitive to alkylating agents, ethyl nitrosourea and N-methyl-N'-nitrosoguanidine. Although no difference was observed in the initial yields of DNA dsbs induced by BLM between LEC and WKAH cells, the repair process of DNA dsbs was significantly slower in LEC cells than WKAH cells.These results showed that the enhanced cellular sensitivity is segregated from the resistant phenotype of DNA synthesis to DNA-damaging agents. The radioresistant DNA synthesis in LEC cells is thought to be due to the deficiency in the transient cell cycle arrest from the G1 to S phases. Furthermore, it is suggested that abnormality in the repair of DNA dsbs might be associated with the abnormality of DNA recombination process. LEC rat could provide a useful animal model to assist in an understanding of the mechanism of the repair process of the radiation-induced DNA damage including DNA recombination and regulation of the cell cycle.

1.结论：1. LEC系大鼠SV 40大T抗原永生化细胞系（LEC系）对X射线的敏感性高于WKAH系大鼠（WKAH系），但对紫外线的敏感性不高。LEC大鼠细胞系的DNA合成对X射线和紫外线照射的耐受性强于WKAH大鼠.在WKAH细胞中观察到辐射诱导的从G1期到S期的进展延迟（G1停滞），但在LEC细胞中未观察到。照射后WKAH细胞p53蛋白条带强度增加，LEC细胞p53蛋白条带强度无明显变化. LEC大鼠细胞对博莱霉素（BLM）诱导DNA双链断裂（dsbs）和交联剂丝裂霉素C的敏感性是WKAH大鼠细胞的2- 3倍，而它们对烷化剂乙基亚硝基脲和N-甲基-N '-亚硝基胍稍敏感。LEC和WKAH细胞对BLM诱导的DNA双链断裂的起始产量无差异，但DNA双链断裂的修复过程明显慢于WKAH细胞，表明LEC细胞对DNA损伤剂的敏感性增强与DNA合成的抗性表型无关。LEC细胞中的辐射抗性DNA合成被认为是由于G1至S期的短暂细胞周期停滞的缺陷。DNA双链断裂修复异常可能与DNA重组过程异常有关。LEC大鼠为研究辐射损伤后DNA修复过程中DNA重组和细胞周期调控机制提供了一个有用的动物模型。