Evidence map›Paper›PMID 40010373›Full record

ArticleRadiation research2025

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 and 1 more

Abstract read
In one paragraph

Article in Radiation research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
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  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Louis V KunzSector of Radiobiology Applied to Radiotherapy, Radiation Oncology Department, Geneva University Hospital, Geneva, Switzerland.
Robert SchaeferCenter for Proton Therapy, Paul Scherrer Institute, 5323 Villigen PSI, Switzerland.
Houda KacemSector of Radiobiology Applied to Radiotherapy, Radiation Oncology Department, Geneva University Hospital, Geneva, Switzerland.
Jonathan OllivierSector of Radiobiology Applied to Radiotherapy, Radiation Oncology Department, Geneva University Hospital, Geneva, Switzerland.
Michele TognoCenter for Proton Therapy, Paul Scherrer Institute, 5323 Villigen PSI, Switzerland.
Flore ChappuisInstitute of Radiation Physics (IRA), Centre Hospitalier Universitaire Vaudois, Lausanne University Hospital, Lausanne, Switzerland.
Damien WeberCenter for Proton Therapy, Paul Scherrer Institute, 5323 Villigen PSI, Switzerland.
Anthony LomaxCenter for Proton Therapy, Paul Scherrer Institute, 5323 Villigen PSI, Switzerland.
Charles L LimoliDepartment of Radiation Oncology, University of California, Irvine, Irvine, California.
Serena PsoroulasCenter for Proton Therapy, Paul Scherrer Institute, 5323 Villigen PSI, Switzerland.
Marie-Catherine VozeninSector of Radiobiology Applied to Radiotherapy, Radiation Oncology Department, Geneva University Hospital, Geneva, Switzerland.

Funding

Project 4: Mechanistic Basics of FLASH Effect: Role of O2P01CA244091 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI LIMOLI, CHARLES · 2020 to 2024
$9.6M
NCI NIH HHS P01 CA244091
6 · The paper itself

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 ultra-high 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.

Indexed as

DNA BreaksPlasmidsProtonsDose-Response Relationship, RadiationHydrogen-Ion ConcentrationProtons

Identifiers

PMID40010373
PMCPMC12919638

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.