| Wang Yue,Sui Li,Wang Qiaojuan,et al.Comparative study on the radiation damage of proton FLASH irradiation to human hepatocytes and hepatocellular carcinoma cells[J].Chinese Journal of Radiological Medicine and Protection,2025,45(11):1107-1114 |
| Comparative study on the radiation damage of proton FLASH irradiation to human hepatocytes and hepatocellular carcinoma cells |
| Received:March 11, 2025 |
| DOI：10.3760/cma.j.cn112271-20250311-00084 |
| KeyWords:FLASH irradiation Proton Liver Radiation damage Hepatocellular carcinoma |
| FundProject:中国原子能科学研究院核物理所所长基金(11SZJJ-202303) |
| Author Name | Affiliation | E-mail | | Wang Yue | Department of Nuclear Physics, China Institute of Atomic Energy, Beijing 102413, China | | | Sui Li | Department of Nuclear Physics, China Institute of Atomic Energy, Beijing 102413, China | lisui@ciae.ac.cn | | Wang Qiaojuan | Department of Nuclear Physics, China Institute of Atomic Energy, Beijing 102413, China | | | Liu Jiancheng | Department of Nuclear Physics, China Institute of Atomic Energy, Beijing 102413, China | | | Su Peng | Department of Nuclear Physics, China Institute of Atomic Energy, Beijing 102413, China | | | Huang Zhihao | Department of Nuclear Physics, China Institute of Atomic Energy, Beijing 102413, China | |
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| Abstract:: |
| Objective To investigate the differential effects of proton FLASH irradiation and conventional dose rate (CONV) irradiation on human normal liver cells WRL68 and human hepatocellular carcinoma cells HepG2. Methods Using a 100 MeV high-current proton cyclotron accelerator, WRL68 and HepG2 cells were subjected to CONV (0.8 Gy/min) and FLASH (40 Gy/s) irradiation with 4 Gy protons. After irradiation, changes in cell proliferation, apoptosis, and cell cycle arrest were detected at different time points. Additionally, transcriptome sequencing was employed to analyze alterations in the gene expression profiles of the two cell lines. Results For WRL68 cells, compared with CONV irradiation, proton FLASH irradiation enhanced cell proliferative activity (t=10.18-16.67, P<0.05), reduced the apoptotic rate (t=3.21-8.30, P<0.05), and decreased the proportion of cells arrested in the G2 phase at the same time points (t=34.08-65.16, P<0.05). In contrast, for HepG2 cells, proton FLASH irradiation significantly inhibited cell proliferation (t=2.57-9.39, P<0.05), increased the apoptotic rate (t=3.25-66.70, P<0.05), and similarly induced cell cycle arrest predominantly in the G2 phase (t=10.87-27.47, P<0.05). Transcriptome sequencing identified 906 differentially expressed genes (DEGs) between the FLASH group and the CONV group in WRL68 cells, and 1 243 DEGs were detected in HepG2 cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of these DEGs suggested that cellular adhesion and oxygen effect may serve as crucial microscopic mechanisms underlying FLASH radiotherapy. Conclusions Under proton FLASH irradiation, the radiation-induced damage to human normal liver cells was significantly alleviated, whereas the damage to hepatocellular carcinoma cells was aggravated. The identified DEGs are involved in multiple radiobiological functional pathways. |
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