Abstract
Ionizing radiation induces DNA double strand breaks (DSBs). Activated ATM phosphorylates H2AX, one of a chromatin protein, and phosphorylated H2AX forms focus at DSBs site. Phosphorylated H2AX foci are regarded as a recruiting mediator of repair factor of DSBs. Although most of phosphorylated H2AX foci disappear with repair of DSBs, a few foci are growing to large and remaining a few days after radiation. However, biological significance of residual foci is not clear. Therefore, we examined correlation between residual large foci and cellular radiosensitivity after ionizing radiation.
We examined dynamics of number and size of phosphorylated H2AX foci in X-irradiated human normal diploid fibroblast cells (HE49 and BJ cells) and human tumor cells (HeLa, U251, T24 and H1299). As a result, unirradiated cells had few large foci. On the other hand, most of cells, which were irradiated with a 0.1% survival dose, had phosphorylated H2AX foci 5 days after irradiation. And these cells stopped their cell division after irradiation.
These results indicate that remained large phosphorylated H2AX foci show loss of proliferating potential after irradiation. Therefore remained foci and cellular radiosensitivity had a close correlation. This suggests that we can use residual phosphorylated H2AX foci to estimate therapy effect of radiotherapy treatment of cancer.
