Origin of genomic instability induced by ionizing radiation

抄録

Ionizing radiation induces DNA double-strand breaks. Recently, it was clarified that frequency of mutation and chromosomal abnormality are significantly elevated among progeny of surviving cells. It is thought that these delayed effects are caused by induction of genomic instability in surviving cells. However mechanisms of maintenance of genomic instability and expression of delayed effects are not made clear. From current results of our research, we expect that origin of genomic instability is a large deletion of genome. To clarify this speculation, we isolated HPRT mutated-clones from X-ray irradiated normal human diploid cells. We analyzed presence of each exson of HPRT gene and size of deletion by using STS markers. Then we analyzed relationship between mutation patterns of HPRT gene and frequency of chromosomal abnormality. These results suggest that delayed chromosomal abnormality is induced by a large deletion of more than 0.5Mb containing HPRT gene. As we expected it, delayed chromosomal abnormality originated from large deletion. In addition, we found that dicentric chromosome without fragment is dominant in delayed chromosomal abnormality. In this paper, we present the character of delayed chromosomal abnormality in survived-clones by using WCP FISH analysis.