Pre-clinical evaluation of lethal and sublethal DNA damage in human cell cultures by ultrashort pulse and ultra-high dose rate laser accelerated protons

Abstract

Particle therapy has been cited as an effective treatment modality, compared to photons and electrons-based therapies for solid tumors located in close proximity to critical organs, such as spinal cord, brain and heart. Numerous studies have demonstrated the feasibility of using high LET particles in tumor cells; however, the very high installation and operational costs limit the utilization of particle therapy.

The idea of future facilities based on laser-driven ion accelerators has been proposed as a way of reducing complexity and cost. Due to the ultra-short duration (10^-12 s) of these beams and their consequent ultra-high dose rates (up to 10^9-10^10 Gy/s), these beams can potentially deliver lethal DNA damaging dose which tumor cells with unstable genome may fail to repair, whilst normal cells are able to repair the same damage.

This Thesis work, carried on in the context of the international A-SAIL (Advanced Strategies for Accelerate Ions with Lasers) project, aims to optimize and validate the dose distribution of laser-driven proton beams at high energies (~10 MeV) and study the effectiveness of these beams in lethal and sub-lethal damage induction in human cells. The effects of the laser driven protons have been investigated in the specific with the study of three endpoints: DNA DSB damage, cell survival and Stress-Induced Premature Senescence (SIPS) in human skin fibroblasts (AG01522) and endothelial cells (HUVEC). Experiments with these beams have been performed in several laser facilities based in the UK (TARANIS, VULCAN) and France (LULI), and results have been compared with outcomes from experiments performed with 225 kVp X-rays (low LET radiation) and α-particles from 5.5 MeV 241Am source, available in PGJCCR (Queen’s University Belfast, Belfast, UK).

Date of Award	Jul 2021
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Engineering and Physical Sciences Research Council & Biotechnology & Biological Sciences Research Council
Supervisor	Marco Borghesi (Supervisor) & Kevin Prise (Supervisor)