Testing chemical carcinogenicity by using a transcriptomics HepaRG-based model?

dc.contributor.authorDoktorova, Tatyana Y.
dc.contributor.authorYildirimman, Reha
dc.contributor.authorCeelen, Liesbeth
dc.contributor.authorVilardell, Mireia
dc.contributor.authorVanhaecke, Tamara
dc.contributor.authorVinken, Mathieu
dc.contributor.authorAtes, Gamze
dc.contributor.authorHeymans, Anja
dc.contributor.authorGmuender, Hans
dc.contributor.authorBort, Roque
dc.contributor.authorCorvi, Raffaella
dc.contributor.authorPhrakonkham, Pascal
dc.contributor.authorLi, Ruoya
dc.contributor.authorMouchet, Nicolas
dc.contributor.authorChesne, Christophe
dc.contributor.authorvan Delft, Joost
dc.contributor.authorKleinjans, Jos
dc.contributor.authorCastell, Jose
dc.contributor.authorHerwig, Ralf
dc.contributor.authorRogiers, Vera
dc.date.accessioned2014-07-25T07:43:59Z
dc.date.available2014-07-25T07:43:59Z
dc.date.issued2014-05-28
dc.description.abstractThe EU FP6 project carcinoGENOMICS explored the combination of toxicogenomics and in vitro cell culture models for identifying organotypical genotoxic- and non-genotoxic carcinogen-specific gene signatures. Here the performance of its gene classifier, derived from exposure of metabolically competent human HepaRG cells to prototypical non-carcinogens (10 compounds) and hepatocarcinogens (20 compounds), is reported. Analysis of the data at the gene and the pathway level by using independent biostatistical approaches showed a distinct separation of genotoxic from non-genotoxic hepatocarcinogens and non-carcinogens (up to 88 % correct prediction). The most characteristic pathway responding to genotoxic exposure was DNA damage. Interlaboratory reproducibility was assessed by blindly testing of three compounds, from the set of 30 compounds, by three independent laboratories. Subsequent classification of these compounds resulted in correct prediction of the genotoxicants. As expected, results on the non-genotoxic carcinogens and the non-carcinogens were less predictive. In conclusion, the combination of transcriptomics with the HepaRG in vitro cell model provides a potential weight of evidence approach for the evaluation of the genotoxic potential of chemical substances.en
dc.identifier.issn1611-2156
dc.identifier.urihttp://hdl.handle.net/2003/33541
dc.identifier.urihttp://dx.doi.org/10.17877/DE290R-857
dc.language.isoen
dc.relation.ispartofseriesEXCLI Journal ; Vol. 13, 2014en
dc.subjectgenotoxic carcinogensen
dc.subjectnon-genotoxic carcinogensen
dc.subjectgene expression profilingen
dc.subjectpathways-based analysisen
dc.subjectHepaRG cell lineen
dc.subjectliver-based in vitro modelsen
dc.subject.ddc610
dc.titleTesting chemical carcinogenicity by using a transcriptomics HepaRG-based model?en
dc.typeText
dc.type.publicationtypearticle
dcterms.accessRightsopen access
eldorado.dnb.zdberstkatid2132560-1

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