S2579
Radiobiology – Normal tissue radiobiology
ESTRO 2026
irradiation. Material/Methods: The study cohort included two mouse strains, C3H/HeNRj and C57BL/6JRj. For each strain, mice were exposed to a single 8 Gy photon irradiation using a 3 mm collimator aperture or left untreated (n=3, respectively). The irradiation target was positioned between the hippocampi, and two opposing beams were applied to achieve homogeneous dose distribution. Brains were collected 24 hours after irradiation, fully sectioned in the axial plane, and stained using immunofluorescence for γ H2AX (DNA double-strand breaks) and DAPI (nuclei). For each mouse, five whole-brain sections within the irradiated region were analyzed. Using a customized Fiji-based program2 nuclear coordinates and sizes, as well as γ H2AX foci number and size per nucleus were extracted. Foci exceeding 11 µm3 were excluded to eliminate pan-nuclear γ H2AX staining artifacts1. The number of foci was corrected (cFoci) to account for the area of individual nuclei and the mean nuclear area per mouse, as described previously4. Results: Using the coordinate data of nuclei, and thus of foci, γ H2AX signals were visualized within the radiation field in whole-brain slices. Overall, there was a higher number of cFoci in irradiated mice compared to controls. In irradiated mice, cortical regions exhibited the lowest cFoci values compared to other brain areas. In C3H/HeNRj mice, cFoci levels were similar across non-cortical regions, whereas in C57BL/6 mice, the hippocampi displayed higher cFoci values than all other regions. Across all analyzed regions, cFoci values were consistently higher in C57BL/6JRj mice than in C3H/HeNRj mice. Conclusion: Regional comparisons of γ H2AX foci revealed distinct radiosensitivity profiles across brain regions, with the cortex exhibiting greater radioresistance. The elevated cFoci counts observed in C57BL/6JRj mice suggest that this strain is more radiosensitive than C3H/HeNRj. References: 1 Suckert et al. 2020 Radiother Oncol May:146:205- 2122 https://github.com/jo-mueller/FociCounter3 Solier & Pommier 2009 Cell Cycle Jun 15;8(12):1853-9 4 Rassamegevanon et al. 2017 Radiother Oncol Sep;124(3):379-385 Keywords: Cranial radiation therapy, sensitivity, DNA damage
polarization with CYNC-1 may represent a promising therapeutic strategy against radiation-induced pulmonary fibrosis. References: 1. Li X, Long Y, Zhu Y, Gu J, Zhou P, Miao C. Endothelial- Derived CCL7 Promotes Macrophage Polarization and Aggravates Septic Acute Lung Injury via CCR1- Mediated STAT1 Succinylation. Adv Sci (Weinh). 2025 Oct; 12(38)2. Rao X, Zhou D, Deng H, Chen Y, Wang J, Zhou X, Jie X, Xu Y, Wu Z, Wang G, Dong X, Zhang S, Meng R, Wu C, Xing S, Fan K, Wu G, Zhou R. Activation of NLRP3 inflammasome in lung epithelial cells triggers radiation-induced lung injury. Respir Res. 2023 Jan 24;24(1):25. 3. Xu Y, Ying L, Lang JK, Hinz B, Zhao R. Modeling mechanical activation of macrophages during pulmonary fibrogenesis for targeted anti- fibrosis therapy. Sci Adv. 2024 Mar 29;10(13) Keywords: macrophage polarization, RILI, CYNC-1 Residual DNA double strand breaks after image- guided radiation indicate differences of regional sensitivity in mouse brains Sindi Nexhipi 1,2 , Laura Pecht 1 , Sebastian Klapputh 1 , Johannes Richard Soltwedel 1,3 , Theresa Suckert 1,2 , Elke Beyreuther 1,4 , Steffen Löck 1,3 , Mechthild Krause 2,5 , Antje Dietrich 1,2 1 OncoRay – National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany. 2 Germany German Cancer Consortium (DKTK), Partner Site Dresden, German Cancer Research Center (DKFZ), Heidelberg, Germany. 3 Institute of Radiooncology – OncoRay, Helmholtz- Zentrum Dresden – Rossendorf Helmholtz-Zentrum Dresden – Rossendorf, Dresden, Germany. 4 Institute of Radiation Physics, Helmholtz-Zentrum Dresden – Rossendorf Helmholtz-Zentrum Dresden – Rossendorf, Dresden, Germany. 5 5. Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany Purpose/Objective: Cranial radiation therapy causes radiation-induced side effects which can lead to neurotoxicity and neurocognitive disorders in cancer survivors. Variations in radiation sensitivity of different brain regions are hypothesized but not yet well understood. We use our preclinical model for image-guided irradiation of mouse brain subvolumes1 to address this question. In this study, we investigate regional variations in radiosensitivity by quantifying residual DNA damage on individual cell level following photon Digital Poster 3699
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