Evidence map›Paper›PMID 35290449›Full record

ArticleRadiation research2022

Mitochondrial Damage Response and Fate of Normal Cells Exposed to FLASH Irradiation with Protons.

Ziyang Guo, Manuela Buonanno, Andrew Harken, Guangming Zhou, Tom K Hei

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Radiation research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
6.6field-weighted citation impact, top 2% of its field
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

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.

  1. The current status of FLASH particle therapy: a systematic review.Physical and engineering sciences in medicine · 2023
    Pooled it
  2. Review
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  5. Article
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  8. Article
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  10. Microenvironmental remodeling in FLASH radiotherapy.Frontiers in cell and developmental biology · 2026
    Review
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  15. Article
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  19. Review
  20. Mechanisms of the FLASH effect: current insights and advances.Frontiers in cell and developmental biology · 2025
    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 at 2 institutions in 2 countries.

Ziyang GuoCenter for Radiological Research, College of Physician and Surgeons, Columbia University Medical Center, New York, New York.
Manuela BuonannoCenter for Radiological Research, College of Physician and Surgeons, Columbia University Medical Center, New York, New York.
Andrew HarkenCenter for Radiological Research, College of Physician and Surgeons, Columbia University Medical Center, New York, New York.
Guangming ZhouState Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Institute of Space Life Sciences, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou 215123, China.
Tom K HeiCenter for Radiological Research, College of Physician and Surgeons, Columbia University Medical Center, New York, New York.
Columbia University Irving Medical Center · USSoochow University · CN

Funding

Flexible Tools for Pre-Clinical Studies to Answer Key Questions UnderlyingHeavy-Ion RadiotherapyU01CA236554 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BRENNER, DAVID JONATHAN, HILLMAN, ELIZABETH M. C. · 2019 to 2022
$2.6M
NCI NIH HHS U01 CA236554
6 · The paper itself

Abstract

Radiation therapy (RT) plays an important role in cancer treatment. The clinical efficacy of radiation therapy is, however, limited by normal tissue toxicity in areas surrounding the irradiated tumor. Compared to conventional radiation therapy (CONV-RT) in which doses are typically delivered at dose rates between 0.03-0.05 Gy/s, there is evidence that radiation delivered at dose rates of orders of magnitude higher (known as FLASH-RT), dramatically reduces the adverse side effects in normal tissues while achieving similar tumor control. The present study focused on normal cell response and tested the hypothesis that proton-FLASH irradiation preserves mitochondria function of normal cells through the induction of phosphorylated Drp1. Normal human lung fibroblasts (IMR90) were irradiated under ambient oxygen concentration (21%) with protons (LET = 10 keV/µm) delivered at dose rates of either 0.33 Gy/s or 100 Gy/s. Mitochondrial dynamics, functions, cell growth and changes in protein expression levels were investigated. Compared to lower dose-rate proton irradiation, FLASH-RT prevented mitochondria damage characterized by morphological changes, functional changes (membrane potential, mtDNA copy number and oxidative enzyme levels) and oxyradical production. After CONV-RT, the phosphorylated form of Dynamin-1-like protein (p-Drp1) underwent dephosphorylation and aggregated into the mitochondria resulting in mitochondria fission and subsequent cell death. In contrast, p-Drp1 protein level did not significantly change after delivery of similar FLASH doses. Compared with CONV irradiation, FLASH irradiation using protons induces minimal mitochondria damage; our results highlight a possible contribution of Drp1-mediated mitochondrial homeostasis in this potential novel cancer treatment modality.

Indexed as

NeoplasmsProton TherapyCell ProliferationFibroblastsHumansProtonsProtons

Identifiers

PMID35290449
PMCPMC9241019
OpenAlexW4220771413

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.