Radiation-induced delayed chromosomal instability caused by large deletion

We examined here whether X-ray-induced gene deletion at the HPRT locus induces delayed instability in the X-chromosome. SV40-immortalized normal human fibroblasts, GM638, were irradiated with 3 Gy of X-rays, and the HPRT mutants were isolated in a medium containing 60 muM of 6-thioguanine. The molecular structure of the HPRT mutations was determined by a multiplex polymerase chain reaction of the nine exons of the HPRT gene. Delayed chromosomal instability in the X-chromosome was analyzed by whole human X-chromosome paint FISH. GM638 and spontaneous mutants, which showed no detectable change, did not induce delayed chromosomal rearrangements; however, all mutants with large deletions showed delayed instability. These results suggest that ionizing radiation-induced large deletion, which alters chromosome structure, is involved in the initiation and perpetuation of radiation-induced genomic instability. (C) 2003 Elsevier B.V. All rights reserved.