Relevance of In Vitro Transcriptomics for In Vivo Mode of Action Assessment
| Autor: | Harm J. Heusinkveld, Emiel Rorije, Paul F.K. Wackers, Jeroen L. A. Pennings, Mirjam Luijten |
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| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
Chemistry Mechanism (biology) General Medicine Computational biology 010501 environmental sciences Toxicology 01 natural sciences In vitro Transcriptome 03 medical and health sciences In vivo Rat liver Toxicogenomics Mode of action 030304 developmental biology 0105 earth and related environmental sciences |
| Zdroj: | Chemical Research in Toxicology. 34:452-459 |
| ISSN: | 1520-5010 0893-228X |
| DOI: | 10.1021/acs.chemrestox.0c00313 |
| Popis: | Recently, we reported an in vitro toxicogenomics comparison approach to categorize chemical substances according to similarities in their proposed toxicological modes of action. Use of such an approach for regulatory purposes requires, among others, insight into the extent of biological concordance between in vitro and in vivo findings. To that end, we applied the comparison approach to transcriptomics data from the Open TG-GATEs database for 137 substances with diverging modes of action and evaluated the outcomes obtained for rat primary hepatocytes and for rat liver. The results showed that a relatively small number of matches observed in vitro were also observed in vivo, whereas quite a large number of matches between substances were found to be relevant solely in vivo or in vitro. The latter could not be explained by physicochemical properties, leading to insufficient bioavailability or poor water solubility. Nevertheless, pathway analyses indicated that for relevant matches the mechanisms perturbed in vitro are consistent with those perturbed in vivo. These findings support the utility of the comparison approach as tool in mechanism-based risk assessment. |
| Databáze: | OpenAIRE |
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