Abstract
Ionizing radiation cause DNA double strand breaks (DSBs). H2AX that is one of a chromatin protein is phosphorylated by activated ATM and forms foci. Then DSBs are rejoined and most of the initial foci disappear. A few foci are growing to large foci. However, biological significance of remaining large foci is not clear. Therefore, we examined correlation between residual large foci and cellular radiosensitivity after ionizing radiation. Human normal diploid fibroblast cells (HE49) and HeLa cells irradiated X-rays then examined alterations of number and size of phosphorylated H2AX foci. We used replicating protein A (RPA) and methylated histone H3 as markers of S-G2 and G1 phase, respectively.
As a result, unirradiated cells had few large foci. And also cells, which stopped their cell division after irradiation, had few large foci. These results indicate that remained large phosphorylated H2AX foci show loss of proliferating potential after irradiation. This suggests that we can use large phosphorylated H2AX foci to estimate therapy effect of radiotherapy treatment of cancer.
