S2576
Radiobiology – Normal tissue radiobiology
ESTRO 2026
University, Aarhus, Denmark, Aarhus University, Aarhus, Denmark. 3 Department of Oncology, Experimental Clinical Oncology, Aarhus University Hospital c Department of Clinical Medicine, Aarhus University, Aarhus, Denmark, Aarhus University, aarhus, Denmark. 4 Aarhus University, Aarhus University, aarhus, Denmark. 5 a Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark b Department of Oncology, Experimental Clinical Oncology, Aarhus University Hospital c Department of Clinical Medicine, Aarhus University, Aarhus, Denmark, Aarhus University, aarhus, Denmark. 6 b Department of Oncology, Experimental Clinical Oncology, Aarhus University Hospital c Department of Clinical Medicine, Aarhus University, Aarhus, Denmark, Aarhus University, Aarhus, Denmark. 7 Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmarkc Department of Clinical Medicine, Aarhus University, Aarhus, Denmarkc Department of Clinical Medicine, Aarhus University, Aarhus, Denmark, Aarhus University, Aarhus, Denmark. 8 Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark, Aarhus University, Aarhus University, Denmark Purpose/Objective: Ultra-high dose-rate irradiation (FLASH) can spare normal tissues while maintaining tumour control compared with conventional dose-rate (CONV) irradiation. Radiolytic oxygen consumption has been proposed as a key mechanism, suggesting that rapid oxygen depletion during irradiation induces transient hypoxia and mediates radioprotection. However, oxygen dynamics during FLASH under hypoxic conditions remain poorly understood. This study aimed to assess how tissue oxygen tension (pO ₂ ) is affected by FLASH under normoxia and hypoxia and evaluate its correlation with acute skin damage Material/Methods: Oxygen dynamics in unanesthetized female C3H/HeNRj mice were assessed using time resolved phosphorescence-lifetime oximetry at 20Hz to measure pO ₂ during 16MeV FLASH electron beam irradiation (231.4 Gy/s) using 61Gy for hypoxic murine legs and 44Gy for normoxic legs. Hypoxia was induced by applying a thigh clamp to restrict blood flow for at least 10 minutes before and during irradiation. Animals were irradiated up to three times, with each pO ₂ recording included as an independent data point (n = 27 irradiations). For CONV irradiation (0.16 Gy/s), pO ₂ was similarly measured, and since no change in pO ₂ was detected during exposure, the pre-irradiation pO ₂ values were used to represent the level during irradiation. Phosphorescence decay curves that were
terms. This was supported by expression analysis of interferon-stimulated genes (ISGs) and transcription factors downstream of IFN-I release, including downstream (p-)STAT1 elevation and increases in INF- stimulated MX1 and RIG-I protein expression in both glandular types. Surprisingly, while INF- β exhibited a protective effect against apoptosis, it also concurrently reduced the potency of thyroid stem/progenitor cells, but increased OFE as a measure of the potency of salivary gland stem/progenitor cells. Conclusion: These results highlight the role of INF- β signalling as a key mediator of radiation-induced inflammation in both the thyroid and salivary glands. However, it has a different role in cell fate regulation after irradiation: it promotes survival after injury in the thyroid gland but reduces regenerative potential, while the effect is opposite in the salivary gland. This suggests that this pathway is a promising therapeutic target for reducing radiation-induced side effects, although each normal tissue may require a different approach.This work was supported by the Dutch Cancer Society KWF Grant nr: 12092 References: 1. Zanten JV, et al. Optimization of the Production Process of Clinical-Grade Human Salivary Gland Organoid-Derived Cell Therapy for the Treatment of Radiation-Induced Xerostomia in Head and Neck Cancer. Pharmaceutics. 2024 Mar 21;16(3):435. 2. Ogundipe VML, et al. Generation and Differentiation of Adult Tissue-Derived Human Thyroid Organoids. Stem Cell Reports. 2021 Apr 13;16(4):913-925. 3. Cinat D, et al. Notch signaling is a driver of glandular stem cell activity and regenerative migration after damage. EMBO J. 2025 Nov 5. doi: 10.1038/s44318-025-00607- w. Epub ahead of print Keywords: Interferon 1, salivary gland, organoids Proffered Paper 3416 FLASH Irradiation under hypoxia reveals a reversed tissue-sparing effect and altered oxygen dynamics Anna Holtz Holtz Hansen 1 , Brita Singers Sørensen 2 , Valentin Vacari Møller 2 , Morten Busk 3 , Sara Poulsen 4 , Line Kristensen 5 , Cathrine Bang Overgard 5 , Priyanshu Sinhab 6 , Jacob Graversen Johansen 7 , Per Rugaard Poulsen 8 1 Department of Oncology, Experimental Clinical Oncology, Aarhus University Hospital c Department of Clinical Medicine, Aarhus University, Aarhus, Denmark, Aarhus University, Aarhus, Denmark. 2 Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark b Department of Oncology, Experimental Clinical Oncology, Aarhus University Hospital c Department of Clinical Medicine, Aarhus
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