FLASH RT, which employs ultra-high dose rates (UHDR), has shown potential in reducing irradiation-induced damage to normal tissue while maintaining effective tumor targeting. For successful clinical translation, mechanistic explanation behind the so-called FLASH effect has yet to be deciphered and new in vivo model systems for mechanistic studies are therefore of high demand. We investigated the differential effects of UHDR (3000–7000 Gy/s) and conventional (CONV) (0.5 Gy/s) irradiation in D. melanogaster by irradiating adult female flies with 16 MeV and 9 MeV electron beams using an adapted clinical linear accelerator. Substantial lifespan prolongations were observed in single high-dose UHDR-irradiated groups compared to CONV irradiation groups with increasing doses (1000–1500 Gy). Split-dose UHDR irradiation further increased the lifespan compared to single high-dose UHDR irradiation. In addition, climbing deficits were induced by 300 Gy of CONV irradiation, but not by single high-dose UHDR irradiation. Additionally, we identified increased levels of lipid peroxidation in D. melanogaster brains indicating ferroptosis following CONV irradiation, which was not observed after single high-dose UHDR irradiation. Using relevant biological endpoints, we here demonstrate D. melanogaster with its advantageous characteristics to be a highly practical preclinical model organism to mechanistically investigate differential responses to UHDR and CONV irradiation.
Kreuzer et al. (Wed,) studied this question.