Evidence map›Paper›PMID 32910239›Full record

ArticleArchives of toxicology2021

Multiple-endpoint in vitro carcinogenicity test in human cell line TK6 distinguishes carcinogens from non-carcinogens and highlights mechanisms of action.

Katherine E Chapman, Eleanor C Wilde, Fiona M Chapman, Jatin R Verma, Ume-Kulsoom Shah, Leanne M Stannard, Anna L Seager, James A Tonkin, M Rowan Brown, Ann T Doherty and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Archives of toxicology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.4field-weighted citation impact, top 46% 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

4 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
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 2 institutions in 1 country.

Katherine E ChapmanIn Vitro Toxicology Group, Institute of Life Science 1, Swansea University Medical School, Swansea University, Singleton Campus, Swansea, SA2 8PP, UK. K.E.Chapman@swansea.ac.uk.ORCID 0000-0001-6668-0705
Eleanor C WildeIn Vitro Toxicology Group, Institute of Life Science 1, Swansea University Medical School, Swansea University, Singleton Campus, Swansea, SA2 8PP, UK.
Fiona M ChapmanIn Vitro Toxicology Group, Institute of Life Science 1, Swansea University Medical School, Swansea University, Singleton Campus, Swansea, SA2 8PP, UK.
Jatin R VermaIn Vitro Toxicology Group, Institute of Life Science 1, Swansea University Medical School, Swansea University, Singleton Campus, Swansea, SA2 8PP, UK.
Ume-Kulsoom ShahIn Vitro Toxicology Group, Institute of Life Science 1, Swansea University Medical School, Swansea University, Singleton Campus, Swansea, SA2 8PP, UK.
Leanne M StannardIn Vitro Toxicology Group, Institute of Life Science 1, Swansea University Medical School, Swansea University, Singleton Campus, Swansea, SA2 8PP, UK.
Anna L SeagerIn Vitro Toxicology Group, Institute of Life Science 1, Swansea University Medical School, Swansea University, Singleton Campus, Swansea, SA2 8PP, UK.
James A TonkinCollege of Engineering, Swansea University, Bay Campus, Swansea, SA1 8EN, UK.
M Rowan BrownCollege of Engineering, Swansea University, Bay Campus, Swansea, SA1 8EN, UK.
Ann T DohertyDiscovery Safety, AstraZeneca, DSM, Darwin Building, Cambridge Science Park, Milton Road, Cambridge, CB4 0WG, UK.
George E JohnsonIn Vitro Toxicology Group, Institute of Life Science 1, Swansea University Medical School, Swansea University, Singleton Campus, Swansea, SA2 8PP, UK.
Shareen H DoakIn Vitro Toxicology Group, Institute of Life Science 1, Swansea University Medical School, Swansea University, Singleton Campus, Swansea, SA2 8PP, UK.
Gareth J S JenkinsIn Vitro Toxicology Group, Institute of Life Science 1, Swansea University Medical School, Swansea University, Singleton Campus, Swansea, SA2 8PP, UK.
Swansea University · GBAstraZeneca (United Kingdom) · GB

Funding

HCRW_ HS-16-33National Centre for the Replacement, Refinement and Reduction of Animals in Research NC/K500033/1National Centre for the Replacement, Refinement and Reduction of Animals in Research NC/R001375/1
6 · The paper itself

Abstract

Current in vitro genotoxicity tests can produce misleading positive results, indicating an inability to effectively predict a compound's subsequent carcinogenic potential in vivo. Such oversensitivity can incur unnecessary in vivo tests to further investigate positive in vitro results, supporting the need to improve in vitro tests to better inform risk assessment. It is increasingly acknowledged that more informative in vitro tests using multiple endpoints may support the correct identification of carcinogenic potential. The present study, therefore, employed a holistic, multiple-endpoint approach using low doses of selected carcinogens and non-carcinogens (0.001-770 µM) to assess whether these chemicals caused perturbations in molecular and cellular endpoints relating to the Hallmarks of Cancer. Endpoints included micronucleus induction, alterations in gene expression, cell cycle dynamics, cell morphology and bioenergetics in the human lymphoblastoid cell line TK6. Carcinogens ochratoxin A and oestradiol produced greater Integrated Signature of Carcinogenicity scores for the combined endpoints than the "misleading" in vitro positive compounds, quercetin, 2,4-dichlorophenol and quinacrine dihydrochloride and toxic non-carcinogens, caffeine, cycloheximide and phenformin HCl. This study provides compelling evidence that carcinogens can successfully be distinguished from non-carcinogens using a holistic in vitro test system. Avoidance of misleading in vitro outcomes could lead to the reduction and replacement of animals in carcinogenicity testing.

Indexed as

Carcinogenicity TestsEndpoint DeterminationResearch DesignCarcinogensCell Cycle CheckpointsCell LineCell ShapeEnergy MetabolismGene Expression RegulationHumansMicronuclei, Chromosome-DefectiveMicronucleus TestsPhosphorylationRisk AssessmentTumor Suppressor Protein p53CarcinogensTP53 protein, humanTumor Suppressor Protein p53Carcinogenicity testingGenotoxicityIn vitroMultiple endpoints

Identifiers

PMID32910239
PMCPMC7811515
OpenAlexW3086976395

What OpenQuestion holds

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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 OpenQuestion graph.