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

缺乏DNA-PK的SCID细胞对低LET辐射和高LET辐射都高度敏感。由含有DNA-PK结构基因的人8号染色体片段导入的杂交SCID细胞将辐射敏感性恢复到野生亲本细胞的水平。本研究采用X射线(200KV)和碳离子作为重离子粒子(290 MeV/u，50keV/μm)进行高LET辐射，研究了细胞对高LET辐射的敏感性变化，以阐明LET辐射所致DNA损伤的修复过程。研究了高LET辐射对SCID细胞和杂交SCID细胞热处理后放射敏感性的变化。虽然两种细胞株在联合热疗时都表现出放射增敏，但SCID细胞比SCID杂交细胞更敏感。这一结果表明，SCID细胞中存在其他可能对热敏感的DNA修复系统。PI3激酶家族的磷酸化抑制剂Wortmannin被高LET辐射处理。当Wortmannin与放射联合应用时，两种细胞对放射的敏感率均增加。在低、高LET照射条件下，Wortmannin对SCID杂交细胞和SCID细胞的放射增敏比相同，分别为2.5~3.1和1.3~1.4。

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.