Testing Chemical Carcinogenicity by Using a Transcriptomics HepaRG-based Model?

Overview

Journal EXCLI J

Specialty Biology

Date 2015 Sep 30

PMID 26417288

Citations 6

Authors

T Y Doktorova

Reha Yildirimman

Liesbeth Ceelen

Mireia Vilardell

Tamara Vanhaecke

Mathieu Vinken

Gamze Ates

Anja Heymans

Hans Gmuender

Roque Bort

Raffaella Corvi

Pascal Phrakonkham

Ruoya Li

Nicolas Mouchet

Christophe Chesne

Joost van Delft

Jos Kleinjans

Jose Castell

Ralf Herwig

Vera Rogiers

Affiliations

Soon will be listed here.

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.

Citing Articles

Evaluation of functional candidate biomarkers of non-genotoxic hepatocarcinogenicity in human liver spheroid co-cultures.

Dos Santos Rodrigues B, Leroy K, Mihajlovic M, De Boever S, Vanbellingen S, Cogliati B Arch Toxicol. 2023; 97(6):1739-1751.

PMID: 36941454 DOI: 10.1007/s00204-023-03486-4.

Comparative Analysis of Transcriptional Responses to Genotoxic and Non-Genotoxic Agents in the Blood Cell Model TK6 and the Liver Model HepaRG.

Kreuzer K, Sprenger H, Braeuning A Int J Mol Sci. 2022; 23(7).

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Connexin-Based Channel Activity Is Not Specifically Altered by Hepatocarcinogenic Chemicals.

Leroy K, Pieters A, Cooreman A, Van Campenhout R, Cogliati B, Vinken M Int J Mol Sci. 2021; 22(21).

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Flow cytometric micronucleus assay and TGx-DDI transcriptomic biomarker analysis of ten genotoxic and non-genotoxic chemicals in human HepaRG™ cells.

Buick J, Williams A, Gagne R, Swartz C, Recio L, Ferguson S Genes Environ. 2020; 42:5.

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