Abstract
In recent years, it was reported that the frequency of mutation and chromosomal aberrations are significantly elevated among progeny of X-ray survivors in comparison with un-irradiated cells. This phenomenon is called "genomic instability" and it may be an important step of carcinogenesis. It is thought that DNA double strand breaks are essential in order to induce genomic instability, but the mechanism of maintaining instability and expressing delayed effect is still unknown.
Because chromosomal deletion occurs as a result of DNA double strand break repair, we predict that genomic instability is induced by the large-scale structural change which happens after irradiation. To make sure this assumption, we analyzed the size of gene deletion and the chromosomal aberration frequency after irradiation.
In the experiment, we irradiated normal human diploid cells with X-rays and isolated HPRT mutated-clones. Then, we analyzed the abnormal chromosome by using WCP FISH. In addition, we examined presence of each exons of HPRT gene and STS markers to assess the size of gene deletion. In the result, we found out that occurrence rate of chromosomal aberrations in clones with a large deletion (>0.5Mb) rises significantly. Furthermore, we isolated secondary and tertiary clones from primary clones with a large deletion (>0.5Mb), and analyzed occurrence rate of chromosomal aberrations.
As a result, translocation is dominant aberration in primary clones. In secondary and tertiary clones, translocation frequency declined, and dicentric is dominant aberration. Clones with the large deletion induce break of the chromosome and telomeric instability. We also found out that telomeric instability is maintained over a protracted period of time after irradiation.
