ESTRO 2025 - Abstract Book

S3934

Radiobiology - Normal tissue radiobiology

ESTRO 2025

Purpose/Objective: Friedreich’s Ataxia (FA) is a neurodegenerative disease that affects more than 15 000 individuals worldwide. It is a recessive genetic disorder caused by a defect in the FXN gene that codes for the frataxin protein. FA usually develops in children and teens and causes damage to the spinal cord, peripheral nerves and the cerebellum portion of the brain. Some studies have shown that FA cells might exhibit an increase in radiosensitivity. To assess the in vitro radiosensitivity of commercial skin fibroblast cell lines derived from FA patients. Material/Methods: Three FA and two normal human skin fibroblast cell lines were included in this study. MTT and trypan blue assays were conducted to assess cellular metabolic activity and viability. The kinetics of radio-induced DNA double-strand break repair were assessed using anti-pATM and anti-γH2AX immunofluorescence. The clonogenic assay was performed to characterize cellular radiosensitivity. Results: There was no statistically significant difference in the metabolic activity of the five tested cell lines (p>0.05). Without irradiation, the basal number of γH2AX foci was significantly higher in FA cell lines compared to the normal cell lines ( p <0.001), while it was lower 10 minutes after a 2Gy irradiation ( p <0.001). However, 24 hours post-irradiation, the number of residual foci in the FA cell lines was significantly higher than in the normal cell lines ( p <0.001). Additionally, FA cells exhibited a lower number of pATM foci 10 minutes and 1 hour post-irradiation ( p <0.001) (Figure 1). Moreover, at a higher dose of irradiation (6Gy), all three FA cell lines showed lower surviving fraction than the two normal cell lines (Figure 2, p <0.01).