Radiation-induced genomic instability triggered by telomere dysfunction

摘要

To examine the possibility that an irradiated chromosome has the potential to promote genome rearrangement, we investigated the stability of irradiated human chromosomes in unirradiated mouse cells using a chromosome transfer technique. The stability of the irradiated human chromosome was analyzed by fluorescence in situ hybridization (FISH) using a probe specific for the human chromosome. The chromosome analysis revealed that the irradiated human chromosome was rearranged after chromosome transfer in two out of four microcell hybrids examined. This result suggests that the irradiated chromosome per se is unstable, even under the unirradiated environment. To determine the trigger for the delayed chromosome instability by radiation, we analyzed chromosome aberrations by telomere FISH technique, and found that the irradiated chromosome showed frequent end-to-end fusions with positive telomere signals at a fusion point. This suggested that telomeres do not function in preventing fusions, in spite of the presence of telomere sequences. These results indicate that radiation promotes telomere dysfunction and that this dysfunction accelerates genomic instability. Thus, we propose that an irradiated chromosome has an elevated potential to rearrange the chromosome in cis- and also in trans-action, and that this chromosomal instability can be triggered by telomere dysfunction.