Evidence map›Paper›PMID 35315142›Full record

ArticleEnvironmental and molecular mutagenesis2022

AOP report: Development of an adverse outcome pathway for oxidative DNA damage leading to mutations and chromosomal aberrations.

Eunnara Cho, Ashley Allemang, Marc Audebert, Vinita Chauhan, Stephen Dertinger, Giel Hendriks, Mirjam Luijten, Francesco Marchetti, Sheroy Minocherhomji, Stefan Pfuhler and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Environmental and molecular mutagenesis, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
4.1field-weighted citation impact, top 4% 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

21 citing papers in PubMed, 44 citations in OpenAlex.

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  5. Transferability and Reproducibility of the HepaRG CometChip Assay.Environmental and molecular mutagenesis · 2025
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  10. Dose-Related Mutagenic and Clastogenic Effects of Benzo[Environmental science & technology · 2024
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  11. Exploring the role of oxidative stress and mitochondrial dysfunction in β-damascone-induced aneuploidy.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2024
    Article
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  13. Risk assessment of small organoarsenic species in food.EFSA journal. European Food Safety Authority · 2024
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  14. Review
  15. Article
  16. Update of the risk assessment of inorganic arsenic in food.EFSA journal. European Food Safety Authority · 2024
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  17. Review
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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

13 authors at 9 institutions in 5 countries.

Eunnara ChoEnvironmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada.ORCID 0000-0001-9942-0053
Ashley AllemangThe Procter & Gamble Company, Mason, Ohio, USA.ORCID 0000-0002-6799-8675
Marc AudebertToxalim, UMR1331, INRAE, Toulouse, France.ORCID 0000-0001-7898-6912
Vinita ChauhanConsumer and Clinical Radiation Protection Bureau, Health Canada, Ottawa, Ontario, Canada.
Stephen DertingerLitron Laboratories, Rochester, New York, USA.
Giel HendriksToxys, Leiden, The Netherlands.
Mirjam LuijtenCentre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.ORCID 0000-0002-5277-1443
Francesco MarchettiEnvironmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada.ORCID 0000-0002-9435-4867
Sheroy MinocherhomjiAmgen Research, Translational Safety and Bioanalytical Sciences, Amgen Inc., Thousand Oaks, California, USA.
Stefan PfuhlerThe Procter & Gamble Company, Mason, Ohio, USA.
Daniel J RobertsCharles River Laboratories, Skokie, Illinois, USA.
Kristina TrenzIngelheim Pharma GmbH & Co.KG, Biberach, Germany.
Carole L YaukEnvironmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada.ORCID 0000-0002-6725-3454
Health Canada · CAProcter & Gamble (United States) · USAmgen (United States) · USBoehringer Ingelheim (Germany) · DECharles River Laboratories (United States) · USInstitut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement · FRLeiden University · NLLitron Laboratories (United States) · USNational Institute for Public Health and the Environment · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The Genetic Toxicology Technical Committee (GTTC) of the Health and Environmental Sciences Institute (HESI) is developing adverse outcome pathways (AOPs) that describe modes of action leading to potentially heritable genomic damage. The goal was to enhance the use of mechanistic information in genotoxicity assessment by building empirical support for the relationships between relevant molecular initiating events (MIEs) and regulatory endpoints in genetic toxicology. Herein, we present an AOP network that links oxidative DNA damage to two adverse outcomes (AOs): mutations and chromosomal aberrations. We collected empirical evidence from the literature to evaluate the key event relationships between the MIE and the AOs, and assessed the weight of evidence using the modified Bradford-Hill criteria for causality. Oxidative DNA damage is constantly induced and repaired in cells given the ubiquitous presence of reactive oxygen species and free radicals. However, xenobiotic exposures may increase damage above baseline levels through a variety of mechanisms and overwhelm DNA repair and endogenous antioxidant capacity. Unrepaired oxidative DNA base damage can lead to base substitutions during replication and, along with repair intermediates, can also cause DNA strand breaks that can lead to mutations and chromosomal aberrations if not repaired adequately. This AOP network identifies knowledge gaps that could be filled by targeted studies designed to better define the quantitative relationships between key events, which could be leveraged for quantitative chemical safety assessment. We anticipate that this AOP network will provide the building blocks for additional genotoxicity-associated AOPs and aid in designing novel integrated testing approaches for genotoxicity.

Indexed as

Adverse Outcome PathwaysChromosome AberrationsDNAHumansMutationOxidative StressRisk AssessmentDNA

Identifiers

PMID35315142
PMCPMC9322445
OpenAlexW4220819700

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.