AbstractIn recent years, a number of extremely interesting and potentially revolutionary differential biological effects has been reported in the radiobiology community by different groups at increased dose rates (e.g., FLASH effect at FLASH dose rates of 100s-1000s Gy/s). General trends are emerging, but these effects still remain poorly understood and the underlying mechanisms are unclear. This thesis focuses on the biological effects of laser-driven proton bursts delivered at ultra-high dose rates (UHDR) of approximately 1010 Gy/s, and thus not only attempts to elucidate some of these effects, but also explores possible scaling of these effects with increasing.
One of the interesting, and unexpected, results presented in this thesis is apparent divergence of the cell survival and radiation-induced DNA damage at the UHDR. Increased residual DNA damage at 6 and 24 hours post-irradiation was measured in the cells irradiated with the UHDR, while simultaneously, a significant increase of cell survival was detected at the UHDR. This is discussed in detail in the thesis and a hypothesis which could explain the measured data is presented. This hypothesis revolves around a recently discovered cell death mechanism called ferroptosis, and around the innate differential ability of normal vs. cancer cells to regulate labile iron and to clear hydroperoxides, and other radicals, and thus to limit oxidative damage. Additional interesting findings in this thesis include microenvironment-independent (3D vs. 2D) cell killing ability of the UHDR proton bursts, while at the conventional dose rate the response was very much dependent on the microenvironment. These are all summarized and discussed in the last chapter.
|Date of Award
|EC/Horizon 2020 Marie Skłodowska-Curie actions & Northern Ireland Department for the Economy
|Marco Borghesi (Supervisor) & Kevin Prise (Supervisor)
- Ultra-High Dose Rate
- laser-driven proton acceleration
- dose-rate effect
- cell survival