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Involvement of telonomic instability in induction of delayed chromosome aberrations by ionizing radiation

端粒组不稳定性参与电离辐射延迟染色体畸变的诱导

基本信息

批准号：
11680552
负责人：
KODAMA Seiji
金额：
$ 2.37万
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：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11680552/
关键词：
radiation delayed chromosome aberration genetic instability oxidative stress scid mouse telomere telonomic instability FBB cycle 非相同末端結合修復 Telonomic instability 遺伝子不安定性

项目摘要

Ionizing radiation induces genetic instability in the progeny of irradiated cells. To elucidate the role of oxidative stress in the susceptibility to induction of genetic instability by ionizing radiation (IR), we examined X-ray-induced delayed chromosome aberrations in human embryo cells under normally oxygenated (20%) and hypoxic (2%) conditions. The results revealed that hypoxia reduced the delayed chromosome aberrations, suggesting that oxidative stress plays a significant role in the induction of genetic instability by IR.To know the role of repair process for DNA double-strand breaks (DBSs) in the induction of genetic instability, we studied X-ray-induced delayed chromosome aberrations in scid mouse cells, which defect in non-homologous end-joining repair for DSBs. The chromosome analysis revealed that scid cells were 2-fold more susceptible to the induction of delayed dicentric chromosomes than wild-type cells even though they received an equivalent survival dose. This result suggests that the impaired repair for DSBs might contribute to the high susceptibility to the induction of genetic instability. To know the mechanism for the formation of delayed dicentric chromosomes, we examined telomere sequences remained at the junctional position of two chromosomes in the delayed dicentric chromosomes using telomere-FISH (t-FISH) technique. The result showed that X-irradiation enhanced the induction of telomeric fusions where the t- FISH positive signals remained at the junctional position and also that the higher percentage of telomeric fusions in scid cells than in wild-type cells. From these results, we propose that the induction of delayed chromosome aberrations is mediated by fusion-bridge-breakage (FBB) cycle possibly initiated with telonomic instability induced by IR.

电离辐射诱导受辐射细胞后代的遗传不稳定性。为了阐明氧化应激在电离辐射（IR）诱导遗传不稳定性的易感性中的作用，我们研究了正常氧（20%）和缺氧（2%）条件下X射线诱导的人胚胎细胞延迟染色体畸变。结果表明，缺氧减少了延迟染色体畸变，表明氧化应激在诱导遗传不稳定性的IR中起着重要作用。为了了解DNA双链断裂（DBS）修复过程在诱导遗传不稳定性中的作用，我们研究了X射线诱导的scid小鼠细胞延迟染色体畸变，该细胞在非同源末端连接修复DSB中有缺陷。染色体分析显示scid细胞比野生型细胞对延迟双着丝粒染色体诱导的敏感性高2倍，即使它们接受了相同的存活剂量。这一结果表明，受损的修复DSB可能有助于高敏感性的遗传不稳定性的诱导。为了了解延迟双着丝粒染色体的形成机制，我们利用端粒荧光原位杂交（t-FISH）技术检测了延迟双着丝粒染色体中保留在两条染色体交界处的端粒序列。结果表明，X射线照射后，scid细胞端粒融合率明显高于野生型细胞。根据这些结果，我们认为延迟性染色体畸变的诱导是由融合-桥-断裂（FBB）周期介导的，可能是由IR诱导的端粒不稳定性引发的。