Evidence map›Paper›PMID 36497055›Full record

ArticleCells2022

Divergent Molecular and Cellular Responses to Low and High-Dose Ionizing Radiation.

Bharath Sampadi, Sylvia Vermeulen, Branislav Mišovic, Jan J Boei, Tanveer S Batth, Jer-Gung Chang, Michelle T Paulsen, Brian Magnuson, Joost Schimmel, Hanneke Kool and 8 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

9 citing papers in PubMed, 16 citations in OpenAlex.

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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

18 authors at 4 institutions in 5 countries.

Bharath SampadiDepartment of Human Genetics, Leiden University Medical Center, 2333ZC Leiden, The Netherlands.ORCID 0000-0002-0916-1594
Sylvia VermeulenDepartment of Human Genetics, Leiden University Medical Center, 2333ZC Leiden, The Netherlands.
Branislav MišovicDepartment of Human Genetics, Leiden University Medical Center, 2333ZC Leiden, The Netherlands.
Jan J BoeiDepartment of Human Genetics, Leiden University Medical Center, 2333ZC Leiden, The Netherlands.
Tanveer S BatthProteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Science, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
Jer-Gung ChangDepartment of Cell and Chemical Biology, Leiden University Medical Center, 2333ZC Leiden, The Netherlands.
Michelle T PaulsenDepartment of Radiation Oncology, Rogel Cancer Center and Center for RNA Biomedicine, University of Michigan, Ann Arbor, MI 48109, USA.
Brian MagnusonDepartment of Radiation Oncology, Rogel Cancer Center and Center for RNA Biomedicine, University of Michigan, Ann Arbor, MI 48109, USA.
Joost SchimmelDepartment of Human Genetics, Leiden University Medical Center, 2333ZC Leiden, The Netherlands.ORCID 0000-0002-2620-4349
Hanneke KoolDepartment of Human Genetics, Leiden University Medical Center, 2333ZC Leiden, The Netherlands.
Cyriel S OlieDepartment of Human Genetics, Leiden University Medical Center, 2333ZC Leiden, The Netherlands.ORCID 0000-0003-2543-8255
Bart EvertsDepartment of Parasitology, Leiden University Medical Center, 2333ZA Leiden, The Netherlands.
Alfred C O VertegaalDepartment of Cell and Chemical Biology, Leiden University Medical Center, 2333ZC Leiden, The Netherlands.ORCID 0000-0002-7989-0493
Jesper V OlsenProteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Science, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
Mats LjungmanDepartment of Radiation Oncology, Rogel Cancer Center and Center for RNA Biomedicine, University of Michigan, Ann Arbor, MI 48109, USA.
Penny A JeggoGenome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton BN1 9RQ, UK.ORCID 0000-0002-8481-1462
Leon H F MullendersDepartment of Human Genetics, Leiden University Medical Center, 2333ZC Leiden, The Netherlands.
Harry VrielingDepartment of Human Genetics, Leiden University Medical Center, 2333ZC Leiden, The Netherlands.
Leiden University Medical Center · NLUniversity of Michigan · USUniversity of Copenhagen · DKUniversity of Sussex · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cancer risk after ionizing radiation (IR) is assumed to be linear with the dose; however, for low doses, definite evidence is lacking. Here, using temporal multi-omic systems analyses after a low (LD; 0.1 Gy) or a high (HD; 1 Gy) dose of X-rays, we show that, although the DNA damage response (DDR) displayed dose proportionality, many other molecular and cellular responses did not. Phosphoproteomics uncovered a novel mode of phospho-signaling via S12-PPP1R7, and large-scale dephosphorylation events that regulate mitotic exit control in undamaged cells and the G2/M checkpoint upon IR in a dose-dependent manner. The phosphoproteomics of irradiated DNA double-strand breaks (DSBs) repair-deficient cells unveiled extended phospho-signaling duration in either a dose-dependent (DDR signaling) or independent (mTOR-ERK-MAPK signaling) manner without affecting signal magnitude. Nascent transcriptomics revealed the transcriptional activation of genes involved in NRF2-regulated antioxidant defense, redox-sensitive ERK-MAPK signaling, glycolysis and mitochondrial function after LD, suggesting a prominent role for reactive oxygen species (ROS) in molecular and cellular responses to LD exposure, whereas DDR genes were prominently activated after HD. However, how and to what extent the observed dose-dependent differences in molecular and cellular responses may impact cancer development remain unclear, as the induction of chromosomal damage was found to be dose-proportional (10-200 mGy).

Indexed as

DNA Breaks, Double-StrandedRadiation, IonizingG2 Phase Cell Cycle CheckpointsReactive Oxygen SpeciesSignal TransductionReactive Oxygen Speciesantioxidant responsecell signalingDNA damage responseionizing radiationlinear no-thresholdlow dosemitochondriaphosphoproteomicsreactive oxygen speciessignal transduction

Identifiers

PMID36497055
PMCPMC9739411
OpenAlexW4310212352

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.