title: The Vitotox and ToxTracker assays: A two-test combination for quick and reliable assessment of genotoxic hazards.
abstract: To ensure safety for humans, it is essential to characterize the genotoxic potential of new chemical entities, such as pharmaceutical and cosmetic substances. In a first tier, a battery of in vitro tests is recommended by international regulatory agencies. However, these tests suffer from inadequate specificity: compounds may be wrongly categorized as genotoxic, resulting in unnecessary, time-consuming, and expensive in vivo follow-up testing. In the last decade, novel assays (notably, reporter-based assays) have been developed in an attempt to overcome these drawbacks. Here, we have investigated the performance of two in vitro reporter-based assays, Vitotox and ToxTracker. A set of reference compounds was selected to span a variety of mechanisms of genotoxic action and applicability domains (e.g., pharmaceutical and cosmetic ingredients). Combining the performance of the two assays, we achieved 93% sensitivity and 79% specificity for prediction of gentoxicity for this set of compounds. Both assays permit quick high-throughput analysis of drug candidates, while requiring only small quantities of the test substances. Our study shows that these two assays, when combined, can be a reliable method for assessment of genotoxicity hazard.
authors: Department of In Vitro Toxicology and Dermato-cosmetology, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. Electronic address: gamze.ates@vub.ac.be.
authors: Gamze
authors: G
authors: Ates
authors: Department of In Vitro Toxicology and Dermato-cosmetology, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium.
authors: Dorien
authors: D
authors: Favyts
authors: Toxys B.V., Robert Boyleweg 4, 2333 CG, Leiden, The Netherlands.
authors: Giel
authors: G
authors: Hendriks
authors: Toxys B.V., Robert Boyleweg 4, 2333 CG, Leiden, The Netherlands.
authors: Remco
authors: R
authors: Derr
authors: Department of Food, Medicines and Consumer Safety, Unit of Toxicology, Scientific Institute of Public Health (WIV-ISP), Juliette Wytsmanstraat 14, B-1050 Brussels, Belgium.
authors: Birgit
authors: B
authors: Mertens
authors: Department of Food, Medicines and Consumer Safety, Unit of Toxicology, Scientific Institute of Public Health (WIV-ISP), Juliette Wytsmanstraat 14, B-1050 Brussels, Belgium.
authors: Luc
authors: L
authors: Verschaeve
authors: Department of In Vitro Toxicology and Dermato-cosmetology, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium.
authors: Vera
authors: V
authors: Rogiers
authors: Department of Food, Medicines and Consumer Safety, Unit of Toxicology, Scientific Institute of Public Health (WIV-ISP), Juliette Wytsmanstraat 14, B-1050 Brussels, Belgium.
authors: Tatyana
authors: T
authors: Y Doktorova
mesh_terms: D000818:Animals; D004249:DNA Damage; D006801:Humans; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity*; D015203:Reproducibility of Results
chemical_list: D009153:Mutagens
keywords: Genotoxicity; Reporter-based; Screening; ToxTracker; Vitotox