Toyokuni, H., Maruo, A., Suzuki, K. and Watanabe, M. The Contribution of Radiation-Induced Large Deletion of the Genome to Chromosomal Instability. Radiat. Res. 171, 198–203 (2009).

Ionizing radiation is known to induce genomic instability that is transmitted across many generations of the progeny of surviving cells. However, the mechanism underlying the initiation, perpetuation and manifestation of radiation-induced genomic instability remains unclear. We expect that large radiation-induced deletions destabilize the structure of chromatin and that this destabilization is transmitted across many generations and plays a role in the perpetuation of genomic instability. Therefore, in this study, we examined the relationship between deletion size and the frequency of delayed chromosomal aberrations in SV40-immortalized normal human fibroblast (GM638) cells. GM638 cells were irradiated with 3 Gy of X rays, and chromosomal aberrations were analyzed in clones derived after irradiation. To determine the size of each deletion, we isolated mutants of the HPRT gene from the X-irradiated cell population and examined the genes around the HPRT locus, which is located in the q-arm of chromosome X. The results indicated that X chromosomes with large (>0.5 Mb) deletions have a higher probability of exhibiting delayed chromosomal aberrations and that these aberrations were induced more frequently in q-arms than in p-arms. Because no induction of X-chromosomal instability was observed in clones that lacked such large deletions, the present findings suggest that chromosomes with large radiation-induced deletions can be genomically unstable.