No induction of p53 phosphorylation and few focus formation of phosphorylated H2AX suggest efficient repair of DNA damage during chronic low-dose-rate irradiation in human cells.
Human fibroblast cells obtained from a normal individual and immortalized by introduction of the hTERT gene were irradiated with 0 to 5 Gy of acute high-dose-rate radiation (1.8 Gy/min) or chronic low-dose-rate radiation (0.3 mGy/min) in the G0 phase, and p53 activation was studied. After high-dose-rate irradiation, a dose-dependent induction of Ser15 phosphorylation was observed, whereas after low-dose-rate irradiation almost none was observed. Then we analyzed the focus formation of phosphorylated histone H2AX protein, which is closely correlated with the induction of double-strand breaks. High-dose-rate radiation induced a significant number of foci in a dose-dependent manner, whereas, low-dose-rate radiation could induce only a few foci even at the highest dose. These results strongly suggest that DNA damage induced by low-dose-rate radiation such as a double-strand break is efficiently repaired during chronic irradiation.
Ishizaki
Kanji
K
Central Laboratory and Radiation Biology, Aichi Cancer Center Research Institute, Nagoya, Japan. kishizaki@aichi-cc.jp
Hayashi
Yuko
Y
Nakamura
Hideaki
H
Yasui
Yoshihiro
Y
Komatsu
Kenshi
K
Tachibana
Akira
A
D015153:Blotting, Western; D002460:Cell Line; D004249:DNA Damage; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D016192:Resting Phase, Cell Cycle; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014965:X-Rays
C468783:H2AX protein, human; D006657:Histones; D016159:Tumor Suppressor Protein p53