Ultra-high dose rate protons in clinical irradiation suppress DNA single-strand breaks induction in the below nano-second time scale of physicochemical stages

This study investigated the impact of ultra-high dose rate (UHDR) proton radiotherapy on DNA damage compared to conventional dose rate (CONV) radiotherapy. We hypothesized that the unique physicochemical processes associated with UHDR could lead to a reduction of DNA damage. Thus, the aim of this study is to clarify the time scale of the physicochemical processes in which the suppression of SSBs by UHDR proton irradiation occurs. Plasmid DNA (pBR322, 4.3 kbp) was irradiated in Tris-HCl solution at three concentrations: 10, 100, and 900 mM. The time-averaged dose rates were 0.1 Gy/s (CONV) and 50 Gy/s (UHDR). Following irradiation, DNA single-strand breaks (SSBs) and double-strand breaks (DSBs) were quantified using agarose gel electrophoresis. A significant reduction in SSB induction was observed only for DNA solution at the highest concentration (900 mM), which corresponds to a scavenging time of approximately 1 ns. These findings suggest that the suppression of SSB induction at UHDR is primarily due to rapid radical-radical reactions occurring within the first nano-second after irradiation. This study provides further insights into the potential benefits of UHDR radiotherapy for reducing healthy tissue damage.