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

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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.