Evidence map›Paper›PMID 19465456›Full record

ArticleToxicological sciences : an official journal of the Society of Toxicology2009

Characterization and interlaboratory comparison of a gene expression signature for differentiating genotoxic mechanisms.

Heidrun Ellinger-Ziegelbauer, Jennifer M Fostel, Chinami Aruga, Daniel Bauer, Eric Boitier, Shibing Deng, Donna Dickinson, Anne-Celine Le Fevre, Albert J Fornace, Olivier Grenet and 8 more

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Toxicological sciences : an official journal of the Society of Toxicology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

22 citing papers in PubMed, 73 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 11 institutions in 5 countries.

Heidrun Ellinger-ZiegelbauerBayer HealthCare AG, Special Toxicology, 42096 Wuppertal, Germany.
Jennifer M Fostel
Chinami Aruga
Daniel Bauer
Eric Boitier
Shibing Deng
Donna Dickinson
Anne-Celine Le Fevre
Albert J Fornace
Olivier Grenet
Yizhong Gu
Jean-Christophe Hoflack
Masako Shiiyama
Roger Smith
Ronald D Snyder
Catherine Spire
Gotaro Tanaka
Jiri Aubrecht
Novartis (Switzerland) · CHPfizer (United States) · USSanofi (France) · FRBayer (Germany) · DEGeorgetown University · USMitsubishi Tanabe Pharma CorporationRoche (Switzerland) · CHServier (France) · FRSRA International (United States) · USSummit School · USTaiho Pharmaceutical (Japan) · JP

Funding

Intramural NIH HHSPHS HHS HHSN273200700046U
6 · The paper itself

Abstract

The genotoxicity testing battery is highly sensitive for detection of chemical carcinogens. However, it features a low specificity and provides only limited mechanistic information required for risk assessment of positive findings. This is especially important in case of positive findings in the in vitro chromosome damage assays, because chromosome damage may be also induced secondarily to cell death. An increasing body of evidence indicates that toxicogenomic analysis of cellular stress responses provides an insight into mechanisms of action of genotoxicants. To evaluate the utility of such a toxicogenomic analysis we evaluated gene expression profiles of TK6 cells treated with four model genotoxic agents using a targeted high density real-time PCR approach in a multilaboratory project coordinated by the Health and Environmental Sciences Institute Committee on the Application of Genomics in Mechanism-based Risk Assessment. We show that this gene profiling technology produced reproducible data across laboratories allowing us to conclude that expression analysis of a relevant gene set is capable of distinguishing compounds that cause DNA adducts or double strand breaks from those that interfere with mitotic spindle function or that cause chromosome damage as a consequence of cytotoxicity. Furthermore, our data suggest that the gene expression profiles at early time points are most likely to provide information relevant to mechanisms of genotoxic damage and that larger gene expression arrays will likely provide richer information for differentiating molecular mechanisms of action of genotoxicants. Although more compounds need to be tested to identify a robust molecular signature, this study confirms the potential of toxicogenomic analysis for investigation of genotoxic mechanisms.

Indexed as

DNA DamageGene Expression ProfilingLaboratoriesPolymerase Chain ReactionCell Line, TumorCell ProliferationCell SurvivalChromosome AberrationsCisplatinCluster AnalysisDNA AdductsDNA Breaks, Double-StrandedDose-Response Relationship, DrugEtoposideGene Expression RegulationHumansCisplatinDNA AdductsEtoposideMutagensPaclitaxelSodium Chloride

Identifiers

PMID19465456
PMCPMC2734310
OpenAlexW2131754552

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.