Comparative study on the radiation damage of proton FLASH irradiation to human hepatocytes and hepatocellular carcinoma cells
10.3760/cma.j.cn112271-20250311-00084
- VernacularTitle:质子FLASH照射对人肝细胞及肝癌细胞辐射损伤比较
- Author:
Yue WANG
1
;
Li SUI
1
;
Qiaojuan WANG
1
;
Jiancheng LIU
1
;
Peng SU
1
;
Zhihao HUANG
1
Author Information
1. 中国原子能科学研究院，北京 102413
- Publication Type:Journal Article
- Keywords:
FLASH irradiation;
Proton;
Liver;
Radiation damage;
Hepatocellular carcinoma
- From:
Chinese Journal of Radiological Medicine and Protection
2025;45(11):1107-1114
- CountryChina
- Language:Chinese
-
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 G 2 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 G 2 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.
