S2561
Radiobiology – Normal tissue radiobiology
ESTRO 2026
References: 1. Paquette IM, Vogel JD, Abbas MA, Feingold DL, Steele SR, Clinical Practice Guidelines Committee of The American Society of C, et al. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Treatment of Chronic Radiation Proctitis. Dis Colon Rectum. 2018;61(10):1135-40.2. Leite CHB, Lopes CDH, Leite C, Terceiro DA, Lima GS, Freitas JA, et al. A Novel Murine Model of a High Dose Brachytherapy-Induced Actinic Proctitis. Front Oncol. 2022;12:802621.3. Maniar K, Moideen A, Mittal A, Patil A, Chakrabarti A, Banerjee D. A story of metformin- butyrate synergism to control various pathological conditions as a consequence of gut microbiome modification: Genesis of a wonder drug? Pharmacol Res. 2017;117:103-28. Keywords: proctitis, metformin, sodium butyrate Digital Poster 1421 Evaluation of pirfenidone as a novel radioprotectant Hiroshi Doi 1,2 , Saori Tatsuno Imamura 1 , Toshiyuki Minami 3 , Yukinori Matsuo 1 1 Radiation Oncology, Kindai University Faculty of Medicine, Sakai, Japan. 2 Radiology, Wakayama Medical University, Wakayama, Japan. 3 Respiratory Medicine and Hematology, Hyogo Medical University, Nishinomiya, Japan Purpose/Objective: Pirfenidone (PFD) is an anti-fibrotic drug that is approved for the treatment of idiopathic pulmonary fibrosis. The purpose of this study was to evaluate the radioprotective potential of PFD in an animal model. Material/Methods: Male C57BL/6J mice were divided into two groups: an unmedicated group (IR alone) and a PFD-treated group (IR+PFD). PFD was orally administered at a dose of 300 mg/kg six hours before total body irradiation (TBI) of 10 Gy in a single fraction. The mice were sacrificed four hours after irradiation, and the duodenal tissue was harvested for TUNEL staining and immunohistochemistry of ATM and γ H2AX. The number of positively stained cells was counted among 25 cells from the bottom of each crypt. In addition, a total of 50–51 crypts per mouse were analysed.To assess the influence of the timing of PFD administration on the protection of normal intestine, mice were divided into four groups: IR alone (unmedicated), PFD-pre/post (administrated 6 hours before and 24 hours after irradiation), PFD-pre (administrated 6 hours before irradiation only), and PFD-post (administrated 24 hours after irradiation only). The mice received TBI at a dose of 15 Gy in a single fraction and were sacrificed 3.5 days after
irradiation for a crypt survival assay. The number of surviving crypts in eight intestinal slices from each mouse was counted. Results: The IR+PFD group showed a significantly less number of apoptotic cells than the IR alone group (P < 0.001). Apoptosis was suppressed in the lower crypt regions, suggesting protection of intestinal stem cells (Figure A). ATM expression was significantly lower in the IR+PFD group than in the IR alone group (Figure B, P = 0.042), whereas γ H2AX expression was significantly higher in the IR+PFD group than in the IR alone group (Figure C, P < 0.001).In the crypt survival assay, the mean number of surviving crypts per section was 7.5, 16.2, 11.3, and 26.0 in the IR alone, PFD-pre/post, PFD- pre, and PFD-post groups, respectively (Figure D). The PFD-pre/post and PFD-post groups showed significantly higher crypt survival than the IR alone group (* in Figure D; P = 0.007 and 0.019, respectively).
Conclusion: PFD attenuated radiation-induced apoptosis and potentially modulated the DNA damage response, characterised by reduced ATM and sustained γ H2AX expression. Administration of PFD after irradiation provided a stronger radioprotective effect than that before irradiation. PFD could be a radioprotector, mitigating gastrointestinal toxicity following irradiation. Keywords: radioprotectant, radiation biology, pirfenidone Studying the toxicity and radiation-modifying effects of nanoparticles using zebrafish (Danio rerio) embryos Júlia Rita Dudás 1 , Katalin Hideghéty 1,2 , Réka Molnár 1 , Attila Ébert 1 , Róbert Polanek 1 , Károly Mogyorósi 1 , Mónika Kiricsi 3 , Nóra Igaz 3 , Emília Rita Szabó 1 1 Ultrafast Science and Application Division, ELI ALPS, ELI-HU Non-Profit Ltd, Szeged, Hungary. 2 Department of Oncotherapy, University of Szeged, Szeged, Digital Poster 1528
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