S2570
Radiobiology – Normal tissue radiobiology
ESTRO 2026
reduced activation of DSB signaling (Figures 1B and 2B).
Digital Poster 2214
DNA damage response impairment in skin and lung fibroblasts after pediatric radiotherapy in a sheep model Hanine Bou Hadir 1 , Charbel Feghaly 1 , Rafka Challita 2 , Joelle Al Choboq 1 , Jolie Bou-Gharios 1 , Hassan Khayat 2 , Abdo Jurjus 2 , Pierre Sfeir 3 , Wassim Abou-Kheir 2 , Bassem Youssef 1 , Larry Bodgi 1 1 Radiation Oncology, American University of Beirut, Beirut, Lebanon. 2 Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut, Lebanon. 3 DEPARTMENT OF SURGERY, American University of Beirut, Beirut, Lebanon Purpose/Objective: Pediatric patients exposed to radiotherapy (RT) are at high risk of severe long-term complications. A major concern is the development of secondary cancers due to radiation-induced DNA damage and genomic instability. To investigate these late effects, a sheep model was developed to simulate pediatric craniospinal irradiation. Due to the radiation delivery geometry, adjacent normal tissues were also exposed.This study assessed the long-term effects of RT on DNA double-strand break (DSB) repair kinetics in lung and skin fibroblasts derived from irradiated Eight sheep were included: five received RT and three served as unirradiated controls. The treated sheep underwent 8 RT fractions, delivering a total dose of 28 Gy to the spinal thecal sac. Adjacent tissues received either high-dose (HD, >20 Gy) or low-dose (LD, <2 Gy) exposure.Three years post-treatment, skin and lung biopsies were collected from HD and LD regions, and from controls. Primary fibroblasts were isolated, expanded, and established (23 lines: nine controls, six LD, eight HD).To assess DSB repair kinetics, cultured cells were irradiated with 2 Gy X-rays. γ H2AX and pATM immunofluorescence assays quantified foci at baseline and 10 min, 1 h, 4 h, and 24 h post- irradiation. Results: Under baseline conditions, LD and HD lung fibroblasts had significantly more spontaneous γ H2AX foci than controls (p < 0.05), indicating enhanced genomic instability (Figure 1A). Ten minutes after 2 Gy irradiation, LD lung fibroblasts showed fewer γ H2AX foci than controls (49 ± 1.6 vs. 60.7 ± 1.8; p < 0.05), whereas skin fibroblasts showed no difference. At 24 h post-irradiation, residual γ H2AX foci remained elevated in fibroblasts from previously irradiated sheep in both tissues (p < 0.001), suggesting impaired DSB repair (Figures 1A and 2A). Additionally, both LD and HD fibroblasts exhibited significantly fewer pATM foci 10 min after irradiation (p < 0.01), indicating and control sheep. Material/Methods:
Figure 1: Average number of γ H2AX foci (A) and pATM foci (B) for control, LD and HD lung fibroblasts (*: p < 0.05; **: p < 0.01; ***: p < 0.001; NS: no significance).
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