Chromosomal Aberrations in Normal and Repair Deficient Cells Exposed to High Dose Rate or Low Dose Rate Irradiation
Ataxia telangiectasia is a human autosomally recessive syndrome characterized by cerebellar ataxia telangiectases, immune dysfunction, and genomic instability, and high rate of cancer incidence.AT cell lines are abnormally sensitive to agents that induce DNA double strand breaks, including ionizing radiation.It has been shown that AT cells contain a large number of unrej oined breaks after both low-dose-rate irradiation and high-dose-rate irradiation, however sensitivity for chromosomal aberrations at low-dose-rate are less often studied.To study how AT cells respond to low-dose-rate irradiation, we exposed confluent normal and AT fibroblast cells to up to 3 Gy of γ-irradiation at a dose rate of 0.5 Gy/day and analyzed chromosomal aberrations in G0 using fusion PCC (Premature Chromosomal Condensation) technique.Giemsa staining showed that 1 Gy induces around 0.36unrejoined fragments per cell in normal cells and around 1.35 fragments in AT cells, whereas 3Gy induces around 0.65 fragments in normal cells and around 3.3 fragments in AT cells.This result indicates that AT cells can rejoin breaks less effectively in G0 phase of the cell cycle compared to normal cells.We also analyzed chromosomal exchanges in normal and AT cells after exposure to 3Gy of low-dose-rate γ rays using a combination of G0 PCC and FISH techniques.Results revealed that normal fibroblasts had no misrejoined breaks after 3 Gy but that AT cells have much more misrejoined breaks during repair under G0 condition.When cells irradiated with 3 Gy were subcultured and G2 chromosomal aberrations were analyzed using calyculin-A induced PCC technique, the yield of unrejoined breaks decreased in both normal and AT cells and misrejoined breaks increased in both cell lines.The present study suggests that AT cells begin to rejoin breaks when a certain number of beaks are accumulated and an increased number of exchanges were observed in G0 AT cells, which is similar situation after high-dose-rate irradiation.
Tetsuya Kawata
国内会议
北京大学医学部放射肿瘤学系成立大会暨北京大学第二届国际放射肿瘤学术论坛
北京
英文
402-402
2012-05-23（万方平台首次上网日期，不代表论文的发表时间）