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Radiosensitivity of Scid Cells Deficient in Repair of DNA Damages Induced by High LET Irradiation

高 LET 辐射诱导的 DNA 损伤修复缺陷的 Scid 细胞的放射敏感性

基本信息

批准号：
12670885
负责人：
OKUMURA Yutaka
金额：
$ 1.66万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670885/
关键词：
scid cells radiosensitivity heavy ion particles DNA double strand breaks DNA-PK activity RBE DNA二重鎖切断

项目摘要

Scid cells deficient in DNA-PK are highly sensitive to low LET radiations as well as high LET radiations. Hybrid scid cells introduced by a fragment of human chromosome 8 which contains the structural gene of DNA-PK recover radiosensitivity to the level of wild parental cells. In this study, changes in radiosensitivity of scid cells to high LET radiation, heavy ion particles, was investigated in order to elucidate the process how DNA damages induced by LET radiation were repaired.X-rays (200 kV) and carbon ions as heavy ion particles (290MeV/u, 50 keV/μm) for high LET radiation were used. Changes in radiosensitivity by heat treatment in scid cells and hybrid scid cells irradiated with high LET radiation were investigated. Although both cell lines showed radiosensitization when heat treatment was combined, scid cells were more sensitized than scid hybrid cells. This result showed that other DNA repair systems exist in scid cells, which might be heat sensitive.Wortmannin, an inhibitor of phosphorylation to PI3 kinase family, was treated with high LET irradiation. Ratio of radiosensitivity was increased when wortmannin was combined with irradiation in both cell lines. The enhancement ratio of radiosensitivity by applying wortmannin was the same for low and high LET irradiation, and was 2.5-3.1 and 1.3 -1.4 for scid hybrid cells and scid cells respectively.

DNA-PK缺陷的Scid细胞对低LET辐射以及高LET辐射高度敏感。将含有DNA-PK结构基因的人类8号染色体片段导入杂交scid细胞，使其放射敏感性恢复到野生亲本细胞的水平。本研究采用X射线（200 kV）和碳离子（290 MeV/u，50 keV/μm）作为高LET辐射的重离子粒子，研究了scid细胞对高LET辐射（重离子粒子）的辐射敏感性变化，以阐明LET辐射诱导的DNA损伤修复过程。本文研究了热处理对scid细胞和杂交scid细胞辐射敏感性的影响。尽管两种细胞系在联合热处理时都表现出放射增敏作用，但scid细胞比scid杂交细胞更敏感。这一结果表明，scid细胞中还存在其他的DNA修复系统，可能是热敏感的。渥曼青霉素与放射线联合应用后，两种细胞株的放射敏感性均增加。wortmannin对低LET和高LET照射的增敏率相同，scid杂交细胞和scid细胞的增敏率分别为2.5-3.1和1.3 - 1.4。