Speaker
Descrizione
Ionizing radiation triggers a sequence of physical, physico-chemical and chemical events from
femtoseconds to milliseconds before entering a biological response window that extends from
seconds to days and years. Within this cascade, superoxide dismutases (SODs) in living cells critically regulate the conversion of superoxide to hydrogen peroxide (H2O2), thereby shaping downstream redox signaling and damage responses. We investigated whether transient pharmacological inhibition of SOD1 prior to irradiation modulated radioprotection under conventional (CONV) and ultra-high dose rate (UHDR) modalities both in vitro and in a in vivo model. Short-term SOD1 inhibition did not impair viability in healthy (HaCaT, 16HBE) and cancer (SAS, SCC25) cell lines, and allowed for enzymatic recovery after drug removal. In vitro irradiation studies using electrons (CONVand UHDR) showed a FLASH-like survival benefit in healthy cells under UHDR, while cancer cells exhibited no protection. Importantly, SOD1 inhibition induced protection in healthy cells also under CONV (electrons, X-Rays) irradiation mode, while cancer cells exhibited no protection. Additionally, in a CAM in vivo model, SOD1 inhibition enhanced embryo survival after both dose rates, without reducing tumor control. These data support SOD1 inhibition as a strategy to modulate early H₂O₂ dynamics, potentially influencing how initial chemical events propagate into subsequent biological responses, and extending FLASH-like radioprotection beyond UHDR.
