| Yang Yuchen,Han Jiaying,Li Xiaobo,et al.Heavy-ion FLASH irradiation mitigates acute intestinal injury and its regulatory mechanisms[J].Chinese Journal of Radiological Medicine and Protection,2025,45(11):1092-1099 |
| Heavy-ion FLASH irradiation mitigates acute intestinal injury and its regulatory mechanisms |
| Received:July 15, 2025 |
| DOI：10.3760/cma.j.cn112271-20250715-00252 |
| KeyWords:Carbon ion radiotherapy FLASH Radiation-induced intestinal injury Double-strand breaks Transcriptomics |
| FundProject:国家重点研发计划(2022YFC2402304);国家自然科学基金(12305410);广州市科技局基础与应用基础研究专题(优秀博士"续航"项目,2025A04J2004) |
| Author Name | Affiliation | E-mail | | Yang Yuchen | Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
United Laboratory of Frontier Radiotherapy Technology of Sun Yat-sen University & Chinese Academy of Sciences Ion Medical Technology Co., Ltd., Guangzhou 510060, China | | | Han Jiaying | Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
United Laboratory of Frontier Radiotherapy Technology of Sun Yat-sen University & Chinese Academy of Sciences Ion Medical Technology Co., Ltd., Guangzhou 510060, China | | | Li Xiaobo | Department of Radiotherapy, Fujian Medical University Union Hospital, Fuzhou 350001, China | | | Zhang Junyu | Department of Radiotherapy, Fujian Medical University Union Hospital, Fuzhou 350001, China | | | Zhou Lirong | Lanzhou Ion Therapy Co., Ltd., Lanzhou 730000, China | | | Shi Jian | Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China | | | Deng Xiaowu | Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
United Laboratory of Frontier Radiotherapy Technology of Sun Yat-sen University & Chinese Academy of Sciences Ion Medical Technology Co., Ltd., Guangzhou 510060, China | | | Zhu Hongyu | Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
United Laboratory of Frontier Radiotherapy Technology of Sun Yat-sen University & Chinese Academy of Sciences Ion Medical Technology Co., Ltd., Guangzhou 510060, China | zhuhy@sysucc.org.cn |
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| Abstract:: |
| Objective To investigate the differences in acute intestinal injury and regulatory mechanisms in mice following carbon ion FLASH radiotherapy (FLASH-RT) and conventional dose rate radiotherapy (CONV-RT). Methods Healthy C57BL/6J mice were randomly divided into three groups: control group, FLASH-RT group (100 Gy/s), and CONV-RT group (0.1 Gy/s), with 9 mice in each group. All mice received carbon ion whole abdominal radiotherapy. DNA double-strand breaks (DSB) and cell proliferation were evaluated by measuring the expression of phosphorylated histone H2AX (γ-H2AX) and nuclear-associated antigen 67 (Ki67) using immunohistochemistry; apoptosis was analyzed using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL); transcriptome sequencing was used to analyze the differences in molecular pathways between FLASH-RT and CONV-RT. Results Compared with the CONV-RT group, the FLASH-RT group showed significantly reduced intestinal γ-H2AX signal at 3 h after radiotherapy (t=3.80, P<0.01), significantly increased expression of Ki67 at the base of intestinal crypts at 6 h after radiotherapy (t=4.30, P<0.001), and a significantly decreased number of TUNEL-positive cells at 12 h after radiotherapy (t=3.08, P<0.01). Transcriptome sequencing analysis showed that FLASH-RT specifically activated the insulin-like growth factor (IGF) pathway, avoiding the excessive activation of CONV-RT-induced nuclear factor-κB and B cell receptor inflammatory pathways as well as the inhibition of energy metabolism. Conclusions Compared with CONV-RT, carbon ion FLASH-RT can reduce DSB damage, preserve the proliferative activity of intestinal stem cells, activate the IGF pathway, and regulate inflammatory, immune, and metabolic pathways, thereby significantly alleviating acute intestinal epithelial injury. Specifically, the regulation of repair pathways mediated by reduced DSB and the inhibition of inflammatory pathways are potential protective mechanisms for normal tissues. |
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