核分裂突变
坏死性下垂
程序性细胞死亡
抗辐射性
衰老
细胞凋亡
有丝分裂
电离辐射
生物
细胞生物学
癌症研究
DNA损伤
细胞培养
脂质过氧化
细胞
氧化应激
辐照
生物化学
遗传学
DNA
核物理学
物理
作者
Sandy Adjemian,Teodora Oltean,Sofie Martens,Bartosz Wiernicki,Vera Goossens,Tom Vanden Berghe,Benjamin Cappe,Maria Ladik,Franck B. Riquet,Liesbeth Heyndrickx,Jolien Bridelance,Marnik Vuylsteke,Katrien Vandecasteele,Peter Vandenabeele
标识
DOI:10.1038/s41419-020-03209-y
摘要
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 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) 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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