Evidence map›Paper›PMID 41003674›Full record

ArticleThe British journal of radiology2026

In vitro oxygen concentration alters reactive oxygen species yields with minor plasmid DNA damage change at ultra-high-dose rate.

William S Thomas, Siddharth Kulkarni, Aleksandra Ilina, Matthew Reed, Brian W Pogue

Abstract read
In one paragraph

Article in The British journal of radiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. BKJournal of neuro-oncology · 2026
    Article
  2. Article
  3. 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

5 authors.

William S ThomasDepartment of Medical Physics, University of Wisconsin-Madison, Madison, WI 53705, United States.ORCID 0009-0005-9829-1794
Siddharth KulkarniDepartment of Medical Physics, University of Wisconsin-Madison, Madison, WI 53705, United States.
Aleksandra IlinaDepartment of Medical Physics, University of Wisconsin-Madison, Madison, WI 53705, United States.ORCID 0000-0003-4537-4519
Matthew ReedDepartment of Medical Physics, University of Wisconsin-Madison, Madison, WI 53705, United States.
Brian W PogueDepartment of Medical Physics, University of Wisconsin-Madison, Madison, WI 53705, United States.ORCID 0000-0002-9887-670X

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Justine Yang Bruce · 1985 to 2026
$142.6M
U.W. RADIOLOGICAL SCIENCES TRAINING PROGRAMT32CA009206 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Bryan Patrick Bednarz · 1985 to 2026
$12.1M
Optimization of MeV FLASH radiotherapy for normal tissue preservationU01CA260446 · NCI · DARTMOUTH COLLEGE · PI David J. Gladstone, Jack Hoopes · 2022 to 2026
$3.1M
Oxygen Dynamics in FLASH RadiotherapyR01CA271330 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Brian William Pogue, Sergei Vinogradov · 2023 to 2026
$2.1M
NCI NIH HHS P30 CA014520NCI NIH HHS R01 CA271330NCI NIH HHS T32 CA009206NCI NIH HHS U01 CA260446NIH HHS R01 CA271330NIH HHS U01 CA260446NIH HHS U24 EB028941-04
6 · The paper itself

Abstract

objectiveUltra-high-dose rate (UHDR) radiotherapy has become a large area of research due to observed normal tissue sparing without sacrificing tumour control, termed the FLASH effect. The purpose of this study was to compare reactive oxygen species (ROS) production and DNA damage across various O2 levels at UHDR and conventional dose rates (CDR) in solutions without repair enzymes and radical scavengers.

methodsSolution assays of both ROS and DNA damage assessed dose rate and oxygen dependent (0%-20% O2) changes between UHDR and CDR from an IntraOp Mobetron. For ROS reporters Amplex UltraRed (H2O2), and CellROX Deep Red (non-H2O2) were quantified via intensity per unit dose. DNA damage assayed plasmid pBR322 gel electrophoresis, to differentiate both single (SSB) and double strand breaks (DSB).

resultsFor ROS assays, a significant reduction was noted from CDR to UHDR across all measured oxygen levels. The generation of H2O2 decreased when departing from physiologically relevant oxygen levels (1%-5%), with generation 30%-40% lower at UHDR. The DNA damage assay showed no trends in the SSB or DSB values with O2.

conclusionExamination of trends between ROS and DNA damage from factors such as oxygen can help elucidate FLASH mechanisms. The H2O2 yield has maximum yield at physiological oxygenation levels (1%-5%), and UHDR further diminishes yield. In DNA damage no trend was observed. It is possible that these mechanisms have underlying effects on the FLASH effect in vivo. ADVANCES IN KNOWLEDGE: This study is the first to directly compare radiation chemistry differences caused by UHDR to biologically relevant DNA damage in identical solutions.

Indexed as

DNA DamageOxygenPlasmidsReactive Oxygen SpeciesDose-Response Relationship, RadiationRadiotherapy DosageOxygenReactive Oxygen SpeciesDNADNA damageelectronFLASHoxygenplasmidUHDR

Identifiers

PMID41003674
PMCPMC13187922

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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.