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Title
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The Vitotox and ToxTracker assays : a two-test combination for quick and reliable assessment of genotoxic hazards
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Author
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Abstract
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| 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. (C) 2016 Elsevier B.V. All rights reserved. |
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Language
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English
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Source (journal)
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Mutation research. Genetic toxicology and environmental mutagenesis. - Amsterdam
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Publication
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Amsterdam
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2016
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ISSN
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1383-5718
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DOI
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10.1016/J.MRGENTOX.2016.09.005
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Volume/pages
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810
(2016)
, p. 13-21
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ISI
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000387525100003
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Pubmed ID
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27776687
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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