Plasmid DNA Strand Breaks Are Dose Rate Independent at Clinically Relevant Proton Doses and Under Biological Conditions

Louis V. Kunz; Robert Schaefer; Houda Kacem; Jonathan Ollivier; Michele Togno; Flore Chappuis; Damien Weber; Anthony Lomax; Charles L. Limoli; Serena Psoroulas; Marie-Catherine Vozenin

doi:10.1667/RADE-24-00118.1

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Louis V. Kunz,^1,2,3,* Robert Schaefer,⁴ Houda Kacem,^1,2,3 Jonathan Ollivier,^1,2,3 Michele Togno,⁴ Flore Chappuis,⁵ Damien Weber,⁴ Anthony Lomax,⁴ Charles L. Limoli,⁶ Serena Psoroulas,⁴ Marie-Catherine Vozenin^1,2,3,**

¹Sector of Radiobiology Applied to Radiotherapy, Radiation Oncology Department, Geneva University Hospital, Geneva, Switzerland
²LiRR - Laboratory of Innovation in Radiobiology Applied to Radiotherapy, Faculty of Medicine, University of Geneva, Geneva, Switzerland
³Laboratory of Radiation Oncology, Radiation Oncology Service, Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
⁴Center for Proton Therapy, Paul Scherrer Institute, 5323 Villigen PSI, Switzerland
⁵Institute of Radiation Physics (IRA), Centre Hospitalier Universitaire Vaudois, Lausanne University Hospital, Lausanne, Switzerland
⁶Department of Radiation Oncology, University of California, Irvine, Irvine, California

^*Radiation Research Society Scholar-in-Training.
^**Corresponding author: Marie-Catherine Vozenin, Sector of Radiobiology Applied to Radiotherapy, Radiation Oncology Department, Geneva University Hospital, Geneva, Switzerland; email: marie-catherine.vozenin@hug.ch.

Abstract

We investigated the effect of proton FLASH radiation on plasmid DNA. Purified supercoiled pBR322 plasmids were irradiated with clinical doses (≤10 Gy) of protons at ultrahigh and conventional dose rates using the Paul Scherrer Institute (PSI) isochronous cyclotron. The proton beam in this clinical facility has been validated to produce the FLASH effect in preclinical models. Plasmid samples were irradiated under various oxygen tensions, scavenger levels, pH conditions and Fe (II) concentrations as these biochemical parameters vary across tissues and tumors. Over the range of doses used, plasmid DNA strand breaks were found to be dose rate independent at all conditions investigated. Irradiation within the Bragg peak and spread-out Bragg peak increased clustered strand breaks, except in the presence of scavengers. With this model system, we demonstrate conclusively that plasmid DNA strand breakage is dose rate independent at doses below 10 Gy and does not constitute a high throughput assay endpoint predictive of the biological effect of FLASH.

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Louis V. Kunz, Robert Schaefer, Houda Kacem, Jonathan Ollivier, Michele Togno, Flore Chappuis, Damien Weber, Anthony Lomax, Charles L. Limoli, Serena Psoroulas, and Marie-Catherine Vozenin "Plasmid DNA Strand Breaks Are Dose Rate Independent at Clinically Relevant Proton Doses and Under Biological Conditions," Radiation Research 203(4), 214-222, (27 February 2025). https://doi.org/10.1667/RADE-24-00118.1

Received: 1 May 2024; Accepted: 13 November 2024; Published: 27 February 2025

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