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

F. Hanton, P. Chaudhary, D. Doria, D. Gwynne, C. Maiorino, C. Scullion, H. Ahmed, T. Marshall, K. Naughton, L. Romagnani, S. Kar, G. Schettino, P. McKenna, S. Botchway, D. R. Symes, P. P. Rajeev, K. M. Prise, M. Borghesi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

LanguageEnglish
Article number4471
Number of pages31
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 14 Mar 2019

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strands
deoxyribonucleic acid
dosage
irradiation
protons
lasers
fibroblasts
kinetics
cells
cyclotrons
therapy
delivery
induction
tumors
ion beams
routes
proteins
costs
photons
x rays

Keywords

  • protontherapy
  • proton delivery
  • laser-based technologies

Cite this

Hanton, F., Chaudhary, P., Doria, D., Gwynne, D., Maiorino, C., Scullion, C., ... Borghesi, M. (2019). DNA DSB repair dynamics following irradiation with laser-driven protons at ultra-high dose rates. Scientific Reports, 9(1), [4471]. https://doi.org/10.1038/s41598-019-40339-6
Hanton, F. ; Chaudhary, P. ; Doria, D. ; Gwynne, D. ; Maiorino, C. ; Scullion, C. ; Ahmed, H. ; Marshall, T. ; Naughton, K. ; Romagnani, L. ; Kar, S. ; Schettino, G. ; McKenna, P. ; Botchway, S. ; Symes, D. R. ; Rajeev, P. P. ; Prise, K. M. ; Borghesi, M. / DNA DSB repair dynamics following irradiation with laser-driven protons at ultra-high dose rates. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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Hanton, F, Chaudhary, P, Doria, D, Gwynne, D, Maiorino, C, Scullion, C, Ahmed, H, Marshall, T, Naughton, K, Romagnani, L, Kar, S, Schettino, G, McKenna, P, Botchway, S, Symes, DR, Rajeev, PP, Prise, KM & Borghesi, M 2019, 'DNA DSB repair dynamics following irradiation with laser-driven protons at ultra-high dose rates' Scientific Reports, vol. 9, no. 1, 4471. https://doi.org/10.1038/s41598-019-40339-6

DNA DSB repair dynamics following irradiation with laser-driven protons at ultra-high dose rates. / Hanton, F.; Chaudhary, P.; Doria, D.; Gwynne, D.; Maiorino, C.; Scullion, C.; Ahmed, H.; Marshall, T.; Naughton, K.; Romagnani, L.; Kar, S.; Schettino, G.; McKenna, P.; Botchway, S.; Symes, D. R.; Rajeev, P. P.; Prise, K. M.; Borghesi, M.

In: Scientific Reports, Vol. 9, No. 1, 4471, 14.03.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - DNA DSB repair dynamics following irradiation with laser-driven protons at ultra-high dose rates

AU - Hanton, F.

AU - Chaudhary, P.

AU - Doria, D.

AU - Gwynne, D.

AU - Maiorino, C.

AU - Scullion, C.

AU - Ahmed, H.

AU - Marshall, T.

AU - Naughton, K.

AU - Romagnani, L.

AU - Kar, S.

AU - Schettino, G.

AU - McKenna, P.

AU - Botchway, S.

AU - Symes, D. R.

AU - Rajeev, P. P.

AU - Prise, K. M.

AU - Borghesi, M.

PY - 2019/3/14

Y1 - 2019/3/14

N2 - 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.

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KW - protontherapy

KW - proton delivery

KW - laser-based technologies

U2 - 10.1038/s41598-019-40339-6

DO - 10.1038/s41598-019-40339-6

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JO - Scientific Reports

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SN - 2045-2322

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