Host: The Japan Radiation Research Society
Co-host: Asian Association for Radiation Research
Ionizing radiation (IR) gives the normal human fibroblasts the phenotype of Senescence-Like Growth Arrest (SLGA), which is a p53-dependent irreversible growth arrest similar to that observed in senescent cells. Recently, it has been reported that IR-induced chromatin alteration activates ATM, suggesting that the residual chromatin alteration may associate with persistent p53 activation. In this report, we examined whether p53 is activated by chromatin damage at the rejoining site of DNA double-strand breaks.
X-irradiation with 4 Gy induced SLGA in 40% and 60% of normal human fibroblasts 4 and 5 days after IR, respectively, while these cells rarely showed SLGA under an unstressed condition. In mitotic cells observed between 4 and 5 days after IR, chromosomal fragments and chromosomal bridges were observed. These mitotic cells with chromosomal aberrations had 2 or 3 phosphorylated histone H2AX foci, and the localization of the foci was both on the intact chromosomes and aberrant chromosome. Especially, frequency of the foci localized on those aberrations was more than 90 % in observed aberration. In the interphase cells 5days after IR, phosphorylated histone H2AX was observed about 4 foci per cell, and all the foci colocalized with phosphorylated ATM foci and phosphorylated p53 at Ser15. These results suggest that cause of persistent activation of p53 could be caused by residual chromatin aberration as well as DNA double-strand break itself.
