Ultrahigh performance liquid chromatography coupled to tandem mass spectrometry was used to quantify the expression of 37 oxylipins derived from eicosatetraenoic, eicosapentaenoic and docosahexaenoic acid in mouse lung and in normal or cancer cells exposed to ultrahigh (FLASH) conventional dose-rate irradiation (CONV) under precise monitoring of the temperature and oxygenation. Among the 37 isomers assayed, 14-16 were present in high enough amount to enable quantitative analysis. The endpoints were the expression of oxylipins as a function of the dose of radiation, hypoxia, temperature and post-irradiation time. In normal, normoxic cells at 37°C radiation elicited destruction and neosynthesis of oxylipins acting antagonistically on a background subject to rapid remodeling by the oxygenases involved in the metabolism of polyunsaturated fatty acids. Neosynthesis occurred in the CONV mode only, in such a way that the level of oxylipins at 5 min after FLASH irradiation was 20-50% lower than in non-irradiated and CONV-irradiated cells. This “FLASH effect” was abolished by lowering the temperature to 20°C and altered by hypoxia in some oxylipins. These patterns were not reproduced in cancer cells, and temperature effects evoke a major difference between normal and tumor cells with regard to the formation and decay of free radical intermediates in phospholipid membranes. Down-regulation of specific oxylipins following FLASH irradiation was also observed in mouse lung at 5 min following irradiation, with near complete recovery in 24 hours and further remodeling at one week and two months post-irradiation.

中文翻译：

---

FLASH 与体外和体内传统剂量率照射后氧脂素库的差异重塑。

采用超高效液相色谱与串联质谱联用，对小鼠肺以及暴露于超高 (FLASH) 常规剂量率照射 (CONV) 的正常或癌细胞中衍生自二十碳四烯酸、二十碳五烯酸和二十二碳六烯酸的 37 种氧脂蛋白的表达进行定量。精确监测温度和氧合。在检测的 37 种异构体中，14-16 种异构体的含量足够高，足以进行定量分析。终点是氧脂质的表达作为辐射剂量、缺氧、温度和辐射后时间的函数。在正常、含氧量正常的细胞中，37°C 辐射会引起氧脂质的破坏和新合成，氧脂质在背景上拮抗作用，经参与多不饱和脂肪酸代谢的加氧酶快速重塑。新合成仅在 CONV 模式下发生，FLASH 照射后 5 分钟时的氧脂质水平比未照射和 CONV 照射的细胞低 20-50%。这种“闪光效应”可通过将温度降低至 20°C 来消除，并通过某些氧脂素中的缺氧而改变。这些模式在癌细胞中没有重现，并且温度效应在磷脂膜中自由基中间体的形成和衰变方面引起正常细胞和肿瘤细胞之间的主要差异。照射后 5 分钟，小鼠肺部也观察到 FLASH 照射后特定氧脂质的下调，24 小时内几乎完全恢复，并在照射后 1 周和 2 个月进一步重塑。