Abstract
X-irradiation induces permanent cell cycle arrest, named senescence-like growth arrest (SLGA), in cells which have unreparable DNA damage. In this study, we compared localization of phosphorylated H2AX and phosphorylated p53 at Ser15 to determine whether ATM-dependent phosphorylation is involved in SLGA. Phosphorylated H2AX formed several speckle foci in all irradiated cells 30 min after 4 Gy irradiation. Phosphorylated p53 was observed at 30 min and discrete foci were formed 2-4 hrs after irradiation. The number of phosphorylated H2AX foci and phosphorylated p53 foci gradually decreased, but large foci were still remained 24hrs after irradiation. Those foci were detected at 5 days post-irradiation, when cells began showing SLGA. Both foci co-localized in more than 80% of cells, although not all the foci were co-localized. These results indicate that ATM-dependent phosphorylation is activated in cells inducing SLGA, however, because not all the phosphorylated p53 co-localized with phosphorylated H2AX foci, other factor(s) may play a role in the induction of SLGA. [J Radiat Res 44:440 (2003)]
