IONIZING RADIATION RESULTS IN A MIXTURE OF CELLULAR OUTCOMES INCLUDING MITOTIC CATASTROPHE, SENESCENCE, METHUOSIS, AND IRON-DEPENDENT CELL DEATH

Ionizing radiation results in a mixture of cellular outcomes including mitotic catastrophe, senescence, methuosis, and iron-dependent cell death

Ionizing radiation results in a mixture of cellular outcomes including mitotic catastrophe, senescence, methuosis, and iron-dependent cell death

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Abstract Radiotherapy is commonly used as a cytotoxic treatment of a wide variety of tumors.Interestingly, few case reports underlined its potential to induce immune-mediated abscopal effects, resulting in regression of metastases, distant from the irradiated site.These observations are rare, and apparently depend on the dose used, suggesting that dose-related cellular responses may be involved in the distant immunogenic responses.Ionizing radiation (IR) has been Tooth Box reported to elicit immunogenic apoptosis, necroptosis, mitotic catastrophe, and senescence.

In order to link a cellular outcome with a particular dose of irradiation, we performed a systematic study in a panel of cell lines on the cellular responses at different doses of X-rays.Remarkably, we observed that all cell lines tested responded in a similar fashion to IR with characteristics of mitotic catastrophe, senescence, lipid peroxidation, and caspase activity.Iron chelators (but not Ferrostatin-1 or vitamin E) Vacuum Pipe could prevent the formation of lipid peroxides and cell death induced by IR, suggesting a crucial role of iron-dependent cell death during high-dose irradiation.We also show that in K-Ras-mutated cells, IR can induce morphological features reminiscent of methuosis, a cell death modality that has been recently described following H-Ras or K-Ras mutation overexpression.

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