<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Ates, Gamze</style></author><author><style face="normal" font="default" size="100%">Birgit Mertens</style></author><author><style face="normal" font="default" size="100%">Heymans, Anja</style></author><author><style face="normal" font="default" size="100%">Luc Verschaeve</style></author><author><style face="normal" font="default" size="100%">Milushev, Dimiter</style></author><author><style face="normal" font="default" size="100%">Vanparys, Philippe</style></author><author><style face="normal" font="default" size="100%">Nancy Roosens</style></author><author><style face="normal" font="default" size="100%">Sigrid C.J. De Keersmaecker</style></author><author><style face="normal" font="default" size="100%">Rogiers, Vera</style></author><author><style face="normal" font="default" size="100%">Tatyana Y. Doktorova</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">A novel genotoxin-specific qPCR array based on the metabolically competent human HepaRG™ cell line as a rapid and reliable tool for improved in vitro hazard assessment</style></title><secondary-title><style face="normal" font="default" size="100%">Archives of Toxicology</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">genotoxicity</style></keyword><keyword><style  face="normal" font="default" size="100%">HepaRG</style></keyword><keyword><style  face="normal" font="default" size="100%">In vitro screening</style></keyword><keyword><style  face="normal" font="default" size="100%">mutagenicity</style></keyword><keyword><style  face="normal" font="default" size="100%">qPCR array</style></keyword><keyword><style  face="normal" font="default" size="100%">Toxicogenomics</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2018</style></year><pub-dates><date><style  face="normal" font="default" size="100%">Jun-02-2018</style></date></pub-dates></dates><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Although the value of the regulatory accepted batteries for in vitro genotoxicity testing is recognized, they result in a high&lt;/p&gt;

&lt;p&gt;number of false positives. This has a major impact on society and industries developing novel compounds for pharmaceutical,&lt;/p&gt;

&lt;p&gt;chemical, and consumer products, as afflicted compounds have to be (prematurely) abandoned or further tested on&lt;/p&gt;

&lt;p&gt;animals. Using the metabolically competent human HepaRG&lt;/p&gt;

&lt;p&gt;™ cell line and toxicogenomics approaches, we have developed&lt;/p&gt;

&lt;p&gt;an upgraded, innovative, and proprietary gene classifier. This gene classifier is based on transcriptomic changes induced by&lt;/p&gt;

&lt;p&gt;12 genotoxic and 12 non-genotoxic reference compounds tested at sub-cytotoxic concentrations, i.e., IC10 concentrations&lt;/p&gt;

&lt;p&gt;as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The resulting gene classifier&lt;/p&gt;

&lt;p&gt;was translated into an easy-to-handle qPCR array that, as shown by pathway analysis, covers several different cellular&lt;/p&gt;

&lt;p&gt;processes related to genotoxicity. To further assess the predictivity of the tool, a set of 5 known positive and 5 known negative&lt;/p&gt;

&lt;p&gt;test compounds for genotoxicity was evaluated. In addition, 2 compounds with debatable genotoxicity data were tested&lt;/p&gt;

&lt;p&gt;to explore how the qPCR array would classify these. With an accuracy of 100%, when equivocal results were considered&lt;/p&gt;

&lt;p&gt;positive, the results showed that combining HepaRG&lt;/p&gt;

&lt;p&gt;™ cells with a genotoxin-specific qPCR array can improve (geno)toxicological&lt;/p&gt;

&lt;p&gt;hazard assessment. In addition, the developed qPCR array was able to provide additional information on compounds&lt;/p&gt;

&lt;p&gt;for which so far debatable genotoxicity data are available. The results indicate that the new in vitro tool can improve human&lt;/p&gt;

&lt;p&gt;safety assessment of chemicals in general by basing predictions on mechanistic toxicogenomics information.&lt;/p&gt;
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