Ren Wenting, Hou Lu, Zhang Ke, Chen Huan, Feng Xin, Jiang Ziming, Shao Fei, Dai Jianrong, Gao Yibo, He Jie
Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Oncol. 2024 Jul 12;14:1442627. doi: 10.3389/fonc.2024.1442627. eCollection 2024.
Current studies have substantiated the sparing effect of ultra-high dose rate irradiation (FLASH) in various organs including the brain, lungs, and intestines. Whether this sparing effect extends to esophageal tissue remains unexplored. This study aims to compare the different responses of esophageal tissue in histological and protein expression levels following conventional dose rate irradiation (CONV) and FLASH irradiation to ascertain the presence of a sparing effect.
C57 female mice were randomly divided into three groups: control, CONV, and FLASH groups. The chest region of the mice in the radiation groups was exposed to a prescribed dose of 20 Gy using a modified electron linear accelerator. The CONV group received an average dose rate of 0.1 Gy/s, while the FLASH group received an average dose rate of 125 Gy/s. On the 10th day after irradiation, the mice were euthanized and their esophagi were collected for histopathological analysis. Subsequently, label-free proteomic quantification analysis was performed on esophageal tissue. The validation process involved analyzing transmission electron microscopy images and utilizing the parallel reaction monitoring method.
Histopathology results indicated a significantly lower extent of esophageal tissue damage in the FLASH group compared to the CONV group ( < 0.05). Label-free quantitative proteomic analysis revealed that the sparing effect observed in the FLASH group may be attributed to a reduction in radiation-induced protein damage associated with mitochondrial functions, including proteins involved in the tricarboxylic acid cycle and oxidative phosphorylation, as well as a decrease in acute inflammatory responses.
Compared with CONV irradiation, a sparing effect on esophageal tissue can be observed after FLASH irradiation. This sparing effect is associated with alleviated mitochondria damage and acute inflammation.
目前的研究已证实超高剂量率照射（FLASH）在包括脑、肺和肠道在内的各种器官中具有保护作用。这种保护作用是否扩展到食管组织仍未得到探索。本研究旨在比较常规剂量率照射（CONV）和FLASH照射后食管组织在组织学和蛋白质表达水平上的不同反应，以确定是否存在保护作用。
将C57雌性小鼠随机分为三组：对照组、CONV组和FLASH组。使用改良的电子直线加速器对辐射组小鼠的胸部区域给予规定剂量20 Gy的照射。CONV组的平均剂量率为0.1 Gy/s，而FLASH组的平均剂量率为125 Gy/s。照射后第10天，对小鼠实施安乐死并收集其食管进行组织病理学分析。随后，对食管组织进行无标记蛋白质组定量分析。验证过程包括分析透射电子显微镜图像和采用平行反应监测方法。
组织病理学结果表明，与CONV组相比，FLASH组食管组织损伤程度明显较低（<0.05）。无标记定量蛋白质组分析显示，FLASH组观察到的保护作用可能归因于与线粒体功能相关的辐射诱导蛋白质损伤的减少，包括参与三羧酸循环和氧化磷酸化的蛋白质，以及急性炎症反应的减少。
与CONV照射相比，FLASH照射后可观察到对食管组织的保护作用。这种保护作用与减轻线粒体损伤和急性炎症有关。
