S2619
Radiobiology - Translational radiobiology
ESTRO 2026
to mutation accumulation and an increased cancer risk. This study aimed to characterize the DSB repair mechanisms in FA cells and evaluate the potential radioprotective effects of Zoledronic acid (Zo) and Pravastatin (Pra), and their combination (ZoPra). Material/Methods: Three FA and two normal human skin fibroblast cell lines were treated with ionizing radiation (IR) alone or following pretreatment for 24 h with 1 or 3 μ M Zoledronic acid (Zo), 1 or 3 μ M Pravastatin (Pra), or their combination (ZoPra). DNA damage response was assessed by immunofluorescence staining using antibodies against pATM, γ -H2AX, 53BP1, and MRE11. Clonogenic assays were conducted to assess cellular radiosensitivity. Results: FA fibroblasts exhibited reduced pATM foci formation at 10 min and 1 h post-IR (p<0.001) and a higher number of residual γ -H2AX foci at 24 h (p<0.001) compared with normal fibroblasts (Figure 1). They also displayed increased 53BP1 and MRE11 foci relative to control fibroblasts, confirming defective DNA-DSB repair mechanism. In normal fibroblasts, Zo, Pra, or ZoPra pretreatments did not significantly alter pATM or γ -H2AX foci numbers compared with 2 Gy alone (p>0.05). Conversely, in FA fibroblasts, Zo and ZoPra pretreatments significantly increased the number of pATM and γ -H2AX foci at 10 min post-IR in FA (p<0.01), while ZoPra significantly reduced residual γ -H2AX foci at 24 h (p<0.05) (Figure 2). Clonogenic assay revealed improved post-irradiation survival in FA fibroblasts following drug pretreatment (p<0.05).
microbiota were collected at defined time points and analyzed using 16S rRNA sequencing and standard protocols. Intestinal lamina propria and epithelial immune cells were isolated, stained with standard immunological markers, and analyzed by flow cytometry. In an orthotopic tumor model, murine intestinal tumor organoids were implanted into HSD- and NSD-fed mice, treated with 5x5 Gy RT and tumor progression and survival was assessed. Results: ModeK cells and organoids cultivated with high NaCl concentrations showed aggravated DNA damage, G2_M arrest, and impaired survival after RT in a dose- dependent manner. Similar effects were observed in vivo, as regeneration after abdominal and total body irradiation was hindered in HSD mice, which correlated with enhanced intestinal permeability. These effects were durable and persisted up to 120 days. An increased amount of T17-helper cells was observed in the ileal LP of HSD mice following RT. Furthermore, microbiome analyses revealed decreased abundances of probiotic taxa in HSD mice, highlighting the crucial role of a well-balanced diet in maintaining intestinal homeostasis. HSD did not improve tumor control following RT. Conclusion: High-salt conditions enhanced tissue injury in vitro and in vivo through increased DNA damage, intestinal dysbiosis, and pathogenic immune priming. These findings indicate that a high-salt diet negatively affects intestinal radiotherapy and support clinical strategies or trials recommending reduced salt consumption. Keywords: intestinal toxicity, diet, microbiome
Digital Poster 2199
DNA double-strand break repair deficiency in Friedreich’s Ataxia: Radioprotective role of Zoledronic Acid and Pravastatin Rafka Salim Challita 1 , Dana Tohme 1 , Leen Abou Najem 1 , Hussein Khram 2 , Walaa Chebli 2 , Gilbert Antaki 1 , Charbel Feghaly 2 , Hanine Bou Hadir 2 , Rana El-
Hassan 1 , Wassim Abou-Kheir 1 , Larry Bodgi 2,1 1 Department of Anatomy, Cell Biology, and
Physiological Sciences, American University of Beirut, Beirut, Lebanon. 2 Department of Radiation Oncology, American University of Beirut Medical Center, Beirut, Lebanon Purpose/Objective: Friedreich’s Ataxia (FA) is a rare neurodegenerative disorder caused by frataxin deficiency, resulting in mitochondrial dysfunction and heightened cellular radiosensitivity. Previous studies have suggested that FA patient–derived cells may exhibit impaired DNA double-strand break (DSB) repair, potentially leading
Figure 1: pATM (A) and γ -H2AX (B) foci kinetics in normal and FA skin fibroblasts following 2 Gy IR. p- values are represented with * or # when comparing with GM03651 or GM03652, respectively.
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