DNA DSB repair dynamics following irradiation with laser-driven protons at ultra-high dose rates

Hanton, F. and Chaudhary, P. and Doria, D. and Gwynne, D. and Maiorino, C. and Scullion, C. and Ahmed, H. and Marshall, T. and Naughton, K. and Romagnani, L. and Kar, S. and Schettino, G. and McKenna, P. and Botchway, S. and Symes, D. R. and Rajeev, P. P. and Prise, K. M. and Borghesi, M. (2019) DNA DSB repair dynamics following irradiation with laser-driven protons at ultra-high dose rates. Scientific Reports, 9 (1). 4471. ISSN 2045-2322 (https://doi.org/10.1038/s41598-019-40339-6)

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Protontherapy has emerged as more effective in the treatment of certain tumors than photon based therapies. However, significant capital and operational costs make protontherapy less accessible. This has stimulated interest in alternative proton delivery approaches, and in this context the use of laser-based technologies for the generation of ultra-high dose rate ion beams has been proposed as a prospective route. A better understanding of the radiobiological effects at ultra-high dose-rates is important for any future clinical adoption of this technology. In this study, we irradiated human skin fibroblasts-AG01522B cells with laser-accelerated protons at a dose rate of 10 9 Gy/s, generated using the Gemini laser system at the Rutherford Appleton Laboratory, UK. We studied DNA double strand break (DSB) repair kinetics using the p53 binding protein-1(53BP1) foci formation assay and observed a close similarity in the 53BP1 foci repair kinetics in the cells irradiated with 225 kVp X-rays and ultra- high dose rate protons for the initial time points. At the microdosimetric scale, foci per cell per track values showed a good correlation between the laser and cyclotron-accelerated protons indicating similarity in the DNA DSB induction and repair, independent of the time duration over which the dose was delivered.