Evidence map›Paper›PMID 26243743›Full record

ArticleMutagenesis2016

Identification of genotoxic compounds using isogenic DNA repair deficient DT40 cell lines on a quantitative high throughput screening platform.

Kana Nishihara, Ruili Huang, Jinghua Zhao, Sampada A Shahane, Kristine L Witt, Stephanie L Smith-Roe, Raymond R Tice, Shunichi Takeda, Menghang Xia

Open access · bronzeAbstract read
In one paragraph

Article in Mutagenesis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

18 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Application of In Vitro Metabolism Activation in High-Throughput Screening.International journal of molecular sciences · 2020
    Review
  5. Review
  6. Article
  7. Review
  8. Review
  9. Genetic toxicology in silico protocol.Regulatory toxicology and pharmacology : RTP · 2019
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Determination of Histone H2AX Phosphorylation in DT40 Cells.Methods in molecular biology (Clifton, N.J.) · 2016
    Article
  18. High-Throughput and High-Content Micronucleus Assay in CHO-K1 Cells.Methods in molecular biology (Clifton, N.J.) · 2016
    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

9 authors at 4 institutions in 2 countries.

Kana NishiharaRadiation Genetics, Graduate School of Medicine, Kyoto University, Yoshidakonoe, Sakyo, Kyoto 606-8501, Japan, National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, MSC: 3375 Bethesda, MD 20892, USA and.
Ruili HuangNational Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, MSC: 3375 Bethesda, MD 20892, USA and.
Jinghua ZhaoNational Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, MSC: 3375 Bethesda, MD 20892, USA and.
Sampada A ShahaneNational Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, MSC: 3375 Bethesda, MD 20892, USA and.
Kristine L WittDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, National Institutes of Health, Research Triangle Park, NC 27709, USA.
Stephanie L Smith-RoeDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, National Institutes of Health, Research Triangle Park, NC 27709, USA.
Raymond R TiceDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, National Institutes of Health, Research Triangle Park, NC 27709, USA.
Shunichi TakedaRadiation Genetics, Graduate School of Medicine, Kyoto University, Yoshidakonoe, Sakyo, Kyoto 606-8501, Japan.
Menghang XiaNational Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, MSC: 3375 Bethesda, MD 20892, USA and mxia@mail.nih.gov.
National Institutes of Health · USNational Center for Advancing Translational Sciences · USKyoto University · JPNational Institute of Environmental Health Sciences · US

Funding

Biomolecular Screening and Alternative Approaches for the National Toxicology ProgramZIAES103318 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI CASEY, WARREN · 2016 to 2021
$25.0M
Toxicology in the 21st Century Program (Tox21) - Systems ToxicologyZIATR000038 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI XIA, MENGHANG · 2015 to 2025
$5.7M
Toxicology in the 21st Century Program (Tox21) - Computational ToxicologyZIATR000040 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI HUANG, RUILI · 2016 to 2025
$3.5M
Toxicology in the 21st Century Program (Tox21) Computational ToxicologyZICTR000040 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI HUANG, RUILI · 2015 to 2015
$50k
6 · The paper itself

Abstract

DNA repair pathways play a critical role in maintaining cellular homeostasis by repairing DNA damage induced by endogenous processes and xenobiotics, including environmental chemicals. Induction of DNA damage may lead to genomic instability, disruption of cellular homeostasis and potentially tumours. Isogenic chicken DT40 B-lymphocyte cell lines deficient in DNA repair pathways can be used to identify genotoxic compounds and aid in characterising the nature of the induced DNA damage. As part of the US Tox21 program, we previously optimised several different DT40 isogenic clones on a high-throughput screening platform and confirmed the utility of this approach for detecting genotoxicants by measuring differential cytotoxicity in wild-type and DNA repair-deficient clones following chemical exposure. In the study reported here, we screened the Tox21 10K compound library against two isogenic DNA repair-deficient DT40 cell lines (KU70 (-/-) /RAD54 (-/-) and REV3 (-/-) ) and the wild-type cell line using a cell viability assay that measures intracellular adenosine triphosphate levels. KU70 and RAD54 are genes associated with DNA double-strand break repair processes, and REV3 is associated with translesion DNA synthesis pathways. Active compounds identified in the primary screening included many well-known genotoxicants (e.g. adriamycin, melphalan) and several compounds previously untested for genotoxicity. A subset of compounds was further evaluated by assessing their ability to induce micronuclei and phosphorylated H2AX. Using this comprehensive approach, three compounds with previously undefined genotoxicity-2-oxiranemethanamine, AD-67 and tetraphenylolethane glycidyl ether-were identified as genotoxic. These results demonstrate the utility of this approach for identifying and prioritising compounds that may damage DNA.

Indexed as

Cell LineDNA Breaks, Double-StrandedAnimalsAntigens, NuclearB-LymphocytesChickensDNA-Binding ProteinsDNA-Directed DNA PolymeraseDNA RepairHigh-Throughput Screening AssaysKu AutoantigenMutagenicity TestsMutagensMutationAntigens, NuclearDNA-Binding ProteinsDNA-Directed DNA PolymeraseKu AutoantigenMutagens

Identifiers

PMID26243743
PMCPMC4723671
OpenAlexW2339107264

What OpenQuestion holds

Textmetadata
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.