Abstract
Ataxia Telangiectasia is a human autosomally recessive syndrome characterized by neurologic degeneration, immune dysfunction, genomic instability, and cancer incidence. AT cell lines exhibit abnormal responses to the agents that induce DNA double strand breaks such as radiation. Using AT and normal human fibroblasts, we have studied the effect of low- and high-LET radiation on the induction of chromosome aberrations. To eliminate the influence from cell cycle progression, cells were irradiated and allowed to repair for 24-h before subculture. Following subculture, FISH painting with chromosome 1 and 3 probes were used. The results showed that chromosome aberrations in AT cells after X-ray irradiation were much more compared to normal cells, especially complex type exchange and unrejoined fragments were much more prevalent for AT cells. However, chromosome aberrations in AT and normal cells exposed to high-LET radiation were found to be similar. It was also found that compare to X-rays much more complex-type exchanges were observed in normal and AT cells and that distribution of aberrations was also found to be very similar. These results suggests that complex-type DNA dsbs induced by high-LET radiations were very difficult to repair correctly. We will also show some data on NBS1 mutant cells exposed to high-LET radiations.
