ArticleClinical and translational radiation oncology2026
Mitochondrial remodeling after conventional and ultra-high dose rate irradiation in head and neck carcinoma cells in vitro.
Article in Clinical and translational radiation oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background and purpose: Ultra-high dose rate (UHDR) irradiation is being investigated as a strategy to widen the therapeutic window of radiotherapy, but the biological mechanisms that distinguish UHDR from conventional dose rate (CONV) irradiation remain unresolved. Because mitochondria integrate bioenergetics, redox control and stress signaling after irradiation, they represent a plausible site at which dose-rate effects could emerge. This study evaluated mitochondrial function after CONV and UHDR irradiation in a head and neck squamous cell carcinoma in vitro model. Materials and methods: LU-HNSCC4 (HN4, an oral cavity HNSCC cell line) cells and VH10 fibroblasts were treated with 0, 2, 6, 10 or 20 Gy delivered at CONV or UHDR using electron irradiation from a modified linear accelerator. High-resolution respirometry was performed immediately after irradiation and 48 h later. In the 0 and 20 Gy groups, flow cytometry was used to assess cellular reactive oxygen species (ROS), mitochondrial ROS (mtROS), mitochondrial membrane potential (MMP) and Magnesium Green fluorescence as an indirect ATP-related readout. RNA sequencing was performed in HN4 cells 48 h after 20 Gy. Results: Irradiation induced clear dose- and time-dependent increases in oxygen consumption in HN4 cells, affecting routine respiration, oxidative phosphorylation capacity and maximal electron transfer capacity. The effect was strongest at higher doses and at 48 h and involved both complex I- and complex II-linked pathways. No statistically significant differences between dose-rate modalities were detected for the principal respiratory endpoints. Flow-cytometric analyses at 20 Gy showed stress responses in both irradiation arms, with some possible differences in temporal pattern; but without a clearly distinct overall phenotype attributable to dose rate. Conclusion: The data support a model in which both CONV and UHDR engage a broadly similar post-irradiation mitochondrial adaptive program in HN4 cells. The findings are relevant to the study of radiation adaptation and support further testing of mitochondria-directed radiosensitization strategies in head and neck cancer.
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