DNA repair defect in AT cells and their hypersensitivity to low-dose-rate radiation.
Ataxia telangiectasia (AT) and normal cells immortalized with the human telomerase gene were irradiated in non-proliferative conditions with high- (2 Gy/min) or low-dose-rate (0.3 mGy/min) radiation. While normal cells showed a higher resistance after irradiation at a low dose rate than a high dose rate, AT cells showed virtually the same survival after low- and high-dose-rate irradiation. Although the frequency of micronuclei induced by low-dose-rate radiation was greatly reduced in normal cells, it was not reduced significantly in AT cells. The number of gamma-H2AX foci increased in proportion to the dose in both AT and normal cells after high-dose-rate irradiation. Although few gamma-H2AX foci were observed after low-dose-rate irradiation in normal cells, significant and dose-dependent numbers of gamma-H2AX foci were observed in AT cells even after low-dose-rate irradiation, indicating that DNA damage was not completely repaired during low-dose-rate irradiation. Significant phosphorylation of ATM proteins was detected in normal cells after low-dose-rate irradiation, suggesting that the activation of ATM plays an important role in the repair of DNA damage during low-dose-rate irradiation. In conclusion, AT cells may not be able to repair some fraction of DNA damage and are severely affected by low-dose-rate radiation.
Central Laboratory and Radiation Biology, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan. hnakumu@aichi-cc.jp
Hideaki
H
Nakamura
Yoshihiro
Y
Yasui
Noriko
N
Saito
Akira
A
Tachibana
Kenshi
K
Komatsu
Kanji
K
Ishizaki
D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000473:pathology; D002460:Cell Line; D002467:Cell Nucleus / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D004247:DNA / Q000235:genetics* / Q000528:radiation effects*; D004249:DNA Damage / Q000235:genetics* / Q000528:radiation effects*; D004260:DNA Repair / Q000235:genetics* / Q000528:radiation effects*; D006657:Histones / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation
C468783:H2AX protein, human; D006657:Histones; D004247:DNA