Abstract
Telomeres, the ends of eukaryotic chromosomes, function to protect chromosome ends from recombination, fusion, and nuclease degradation. Because telomeres consist of G-rich tandem DNA repeats such as TTAGGG, it is assumed that they are liable to the attack by reactive oxygen species. To examine the possibility that radiation damage preferentially accumulates in telomeres, we investigated radiation-induced abnormal telomere signals using telomere fluorescence in situ hybridization (FISH). Normal human fibroblasts were exposed to hydrogen peroxide (200μM, 1h) or 0.5 Gy of X-rays with combined pre- and post-treatment of ascorbic acid (5mM, 2h) at G2 phase, and examined chromosome aberrations, loss of telomere signals (LTS), and extra telomere signals (ETS). The frequency of X-ray-induced chromosome aberrations was 0.83±0.66 per cell, and this was no longer changed by the pre-treatment of ascorbic acid. The exposure to hydrogen peroxide and X-rays did not affect the frequency of LTS. Neither pre-treatment nor post-treatment of ascorbic acid changed the LTS frequency. In contrast, the frequency of ETS was increased by the exposure to hydrogen peroxide and X-rays by three-fold and two-fold, respectively. In addition, X-ray-induced ETS was suppressed at the basal level by the combined post-treatment with ascorbic acid. The present study suggests that the cause of ETS is different from those of chromosome aberrations, which are initiated by DNA double strand breaks, and that the pathway to produce ETS is sensitive to oxidative stress.
