Ionizing radiation (IR) induces various types of damage in the cellular DNA, of which the most deleterious are double strand breaks. Double strand breaks lead to activation of signaling cascade aiming to repair the damage or to transiently or permanently arrest cell cycle, and/or induce cell death. In the case of high doses of ionizing radiation with a high dose-rate (0.5-1 Gy / min) where the cell repair capacity is insufficient, cell death often occurs in response to double-strand breaks. The response to the radiation exposure depends on many factors such as the cell type, its proliferation activity, and p53 status. In tumor cells, cell death is associated primarily with apoptosis or mitotic catastrophe. In normal fibroblasts, cells accumulate in the G1 phase of the cell cycle and so-called premature senescence occurs after irradiation.In cells with functional p53 protein an increase in the p21 protein (cell division inhibitor) and accumulation of the cells in the G1 phase occurs. In the case of very low-dose rate (LDR), this accumulation is transient; after DNA damage repair, the cells continue to divide. Upon irradiation with higher doses at a LDR, accumulation in the G1 phase is irreversible; p16 protein is upregulated and the status of premature senescence is induced.  The same dose of radiation administered at LDRs results in more senescence than after an acute exposure.In the case of the use of IR for the eradication of tumor cells, the status of these cells is important in terms of p53 and proliferation. About fifty percent of tumor cells do not possess p53 protein or are mutant, and after irradiation they accumulate in the G2 phase and repair the IR-induced damage (e.g. HL-60 cells). In HL-60 cells (p53^-/- human promyelocytic leukemia), G2 phase accumulation occurs during irradiation with low dose rate, and their radioresistance increases if the cells are irradiated in the G2-phase. When the dose-rate is very low, the cells enter the mitotic cycle during irradiation, and because cels in mitosis are highly radiosensitive, apoptosis is induced and thus their radiosensitivity increases as well.

Keywords: cell death; apoptosis; senescence; p53; p21; ionizing radiation; dose rate