Involvement of telonomic instability in induction of delayed chromosome aberrations by ionizing radiation
| Project/Area Number |
11680552
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
環境影響評価(含放射線生物学)
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| Research Institution | Nagasaki University |
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Principal Investigator |
KODAMA Seiji Nagasaki University, School of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (00195744)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Keiji Nagasaki University, School of Pharmaceutical Sciences, Research Associate, 薬学部, 助手 (00196809)
WATANABE Masami Nagasaki University, School of Pharmaceutical Sciences, Professor, 薬学部, 教授 (20111768)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | 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 |
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| Research Abstract |
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.
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Report
(3 results)
Research Products
(17 results)
