Fig. 8. Cellular responses to ionizing radiation.

Following X-ray irradiation with doses ranging from 2 to 50 Gy, there is a dose-dependent increase in ROS production, lipid peroxidation, and DNA damage. As a result, the DNA damage response is activated and will attempt to resolve the DNA breaks. In a case of low irradiation dose (<10 Gy), cells manage to repair their DNA, and still retain their capacity to proliferate. Cells with irreparable DNA that go into replication will be stuck in the mitotic cycle and undergo mitotic failure. Cells in a state of mitotic catastrophe will have several fates depending on the extent of the nuclear abnormalities and on the proteins expressed. Several outcomes of mitotic catastrophe seem to co-exist, such as senescence, methuosis, necrosis (membrane permeabilization), and activation of Bax, Bak, and caspases with presence of apoptotic features. A part of the senescent cells might become apoptotic (dotted arrow). K-Ras mutation can induce both senescence and methuosis; however, a link between the two cell states was never described. Here, we found that part of the large cells with flattened morphology also had methuotic vacuoles, which might indicate that methuosis could be an outcome of senescent cells (dotted arrow). Ultimately, the cells will die out of an iron-dependent type of cell death.