High susceptibility and possible involvement of telonomic instability in the induction of delayed chromosome aberrations by X-irradiation in scid mouse cells

摘要

Ionizing radiation induces genetic instability in the progeny of irradiated cells. There is evidence to suggest that DNA double-strand breaks (DSBs) and subsequent repair processes are important in the induction of genetic instability. In the present study, we hypothesize that the impaired repair for DSBs increases the susceptibility to the induction of genetic instability. To examine this hypothesis, we studied delayed chromosome aberrations induced by X-irradiation in scid mouse cells. The chromosome analysis revealed that the scid cells were 2.7-fold more susceptible to the induction of delayed dicentric chromosomes than the wild-type cells, even though they received the equivalent survival dose. In order to find the mechanism for the formation of delayed chromosome aberrations, we examined telomere sequences that remained at the junctional position of two chromosomes in the delayed dicentric chromosomes using the telomere-FISH technique. The scid cells showed a higher percentage of telomeric fusions thanthe wild-type cells. These results suggest that the DNA-de-pendent protein kinase catalytic subunit may be involved in the maintenance of telomere stability. From the results presented here, we propose that the induction of delayed chromosome aberrations is mediated by the fusion-bridge-breakage cycle possibly initiated with telonomic instability, induced by ionizing radiation.