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|Title:||Testing chemical carcinogenicity by using a transcriptomics HepaRG-based model?|
|Authors:||DOKTOROVA Tatyana; YILDIRIMMAN Reha; CEELEN Liesbeth; VILARDELL Mireia; VANHAECKE Tamara; VINKEN Mathieu; ATES Gamze; HEYMANS Anja; GMUENDER Hans; BORT Roque; CORVI Raffaella; PHRAKONKHAM PASCAL; LI Ruoya; MOUCHET Nicolas; CHESNE Christopher; VAN DELFT Joost; KLEINJANS Jos; CASTELL Jose; HERWIG Ralf; ROGIERS Vera|
|Citation:||EXCLI JOURNAL vol. 13 p. 623-637|
|Publisher:||EXCLI JOURNAL MANAGING OFFICE|
|Type:||Articles in periodicals and books|
|Abstract:||The 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.|
|JRC Directorate:||Institute for Health and Consumer Protection Historical Collection|
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