Changes in Yields of Water Radiolysis Species and Strand Breaks of Pbr322 Plasmid DNA under Ultra-high Dose Rate C Ions: Towards the Elucidation of the Mechanism of FLASH Radiotherapy.

Abstract

To clarify the mechanisms of FLASH radiotherapy using C ion beams (373 MeV/u and 90 MeV/u), we investigated the dose rate dependence of yields of water radiolysis species (OH radicals, hydrated electrons, and hydrogen peroxide). Additionally, we evaluated changes in the induction rate of DNA strand breaks as a function of dose rate using pBR322 plasmid DNA in solutions. Average dose rates were 0.2 Gy/s [conventional (CONV)] and 75 Gy/s [ultra-high dose rate (UHDR)] for 373 MeV/u, and 0.3 Gy/s (CONV) and 100 Gy/s (UHDR) for 90 MeV/u. The G values of water radiolysis species decreased with UHDR irradiation compared to CONV dose rate, except for hydrogen peroxide exposed to 90 MeV/u C ions, whose yield remained independent of dose rate. Furthermore, the induction rate of single-strand breaks (SSB) was unaffected by dose rate, while the induction of double-strand breaks (DSB) decreased after UHDR irradiation. These findings suggest that radical-radical reactions occur more efficiently with increasing dose rate, resulting in a reduced contribution of water radiolysis species to DNA strand breaks, especially DSBs, after irradiation with C ions. Therefore, changes in the contribution of water radiolysis species to DNA strand breaks could play a crucial role in the sparing effects observed after UHDR irradiation.