Radiation-induced bystander effect is a biological response in nonirradiated cells receiving signals from cells exposed to ionising radiation. The aim of this in vivo study was to analyse whether extracellular vesicles (EVs) originating from irradiated mice could induce modifications in the redox status and expression of radiation-response genes in bystander mice. C57BL/6 mice were whole-body irradiated with 0.1-Gy and 2-Gy X-rays, and EVs originating from mice irradiated with the same doses were injected into naïve, bystander mice. Lipid peroxidation in the spleen and plasma reactive oxygen metabolite (ROM) levels increased 24 h after irradiation with 2 Gy. The expression of antioxidant enzyme genes and inducible nitric oxide synthase 2 (iNOS2) decreased, while cell cycle arrest-, senescence- and apoptosis-related genes were upregulated after irradiation with 2 Gy. In bystander mice, no significant alterations were observed in lipid peroxidation or in the expression of genes connected to cell cycle arrest, senescence and apoptosis. However, there was a systemic increase in the circulating ROM level after an intravenous EV injection, and EVs originating from 2-Gy-irradiated mice caused a reduced expression of antioxidant enzyme genes and iNOS2 in bystander mice. In conclusion, we showed that ionising radiation-induced alterations in the cellular antioxidant system can be transmitted in vivo in a bystander manner through EVs originating from directly irradiated animals.

中文翻译：

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细胞外囊泡介导的氧化应激和基因表达修饰：辐射诱导的旁观者效应的体内研究。

辐射诱发的旁观者效应是非辐射细胞的生物学反应，该细胞从暴露于电离辐射的细胞接收信号。这项体内研究的目的是分析源自受辐照小鼠的细胞外囊泡（EVs）是否可以诱导旁观者小鼠的氧化还原状态和辐射反应基因表达的改变。用0.1-Gy和2-Gy X射线对C57BL / 6小鼠进行全身照射，并将来自以相同剂量照射的小鼠产生的EV注射到幼稚的旁观者小鼠中。2 Gy照射后24 h，脾脏脂质过氧化和血浆反应性氧代谢产物（ROM）含量增加。抗氧化酶基因和诱导型一氧化氮合酶2（iNOS2）的表达下降，而细胞周期停滞，2 Gy照射后，衰老和凋亡相关基因被上调。在旁观者小鼠中，脂质过氧化作用或与细胞周期停滞，衰老和凋亡相关的基因表达未见明显变化。但是，静脉内注射EV后，循环ROM水平有系统性增加，并且源自2-Gy辐照小鼠的EV导致旁观者小鼠中抗氧化酶基因和iNOS2的表达降低。总之，我们表明，细胞抗氧化剂系统中的电离辐射诱导的改变可以通过直接照射动物产生的电动汽车以旁观者的方式体内传播。脂质过氧化作用或与细胞周期停滞，衰老和凋亡相关的基因表达未见明显变化。但是，静脉内注射EV后，循环ROM水平有系统性增加，并且源自2-Gy辐照小鼠的EV导致旁观者小鼠中抗氧化酶基因和iNOS2的表达降低。总之，我们表明，细胞抗氧化剂系统中的电离辐射诱导的改变可以通过直接照射动物产生的电动汽车以旁观者的方式体内传播。脂质过氧化作用或与细胞周期停滞，衰老和凋亡相关的基因表达未见明显变化。但是，静脉内注射EV后，循环ROM水平有系统性增加，并且源自2-Gy辐照小鼠的EV导致旁观者小鼠中抗氧化酶基因和iNOS2的表达降低。总之，我们表明，细胞抗氧化剂系统中的电离辐射诱导的改变可以通过直接照射动物产生的电动汽车以旁观者的方式体内传播。