Application of the comparison approach to open TG-GATEs: A useful toxicogenomics tool for detecting modes of action in chemical risk assessment.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsHeusinkveld, Harm J
Wackers, Paul Fk
Schoonen, Willem G
van der Ven, Leo
Pennings, Jeroen LA
MetadataShow full item record
TitleApplication of the comparison approach to open TG-GATEs: A useful toxicogenomics tool for detecting modes of action in chemical risk assessment.
Published inFood Chem Toxicol 2018; advance online publication (ahead of print)
PubliekssamenvattingMode of action information is one of the key components for chemical risk assessment as mechanistic insight leads to better understanding of potential adverse health effects of a chemical. This insight greatly facilitates assessment of human relevance and enhances the use of non-animal methods for risk assessment, as it ultimately enables extrapolation from initiating events to adverse effects. Recently, we reported an in vitro toxicogenomics comparison approach to categorize (non-)genotoxic carcinogens according to similarities in their proposed modes of action. The present study aimed to make this comparison approach generally applicable, allowing comparison of outcomes across different studies. The resulting further developed comparison approach was evaluated through application to toxicogenomics data on 18 liver toxicants in human and rat primary hepatocytes from the Open TG-GATEs database. The results showed sensible matches between compounds with (partial) overlap in mode of action, whilst matches for compounds with different modes of action were absent. Comparison of the results across species revealed pronounced and relevant differences between primary rat and human hepatocytes, underpinning that information on mode of action enhances assessment of human relevance. Thus, we demonstrate that the comparison approach now is generally applicable, facilitating its use as tool in mechanism-based risk assessment.
- A novel transcriptomics based in vitro method to compare and predict hepatotoxicity based on mode of action.
- Authors: De Abrew KN, Overmann GJ, Adams RL, Tiesman JP, Dunavent J, Shan YK, Carr GJ, Daston GP, Naciff JM
- Issue date: 2015 Feb 3
- A novel toxicogenomics-based approach to categorize (non-)genotoxic carcinogens.
- Authors: Schaap MM, Wackers PF, Zwart EP, Huijskens I, Jonker MJ, Hendriks G, Breit TM, van Steeg H, van de Water B, Luijten M
- Issue date: 2015 Dec
- DTNI: a novel toxicogenomics data analysis tool for identifying the molecular mechanisms underlying the adverse effects of toxic compounds.
- Authors: Hendrickx DM, Souza T, Jennen DGJ, Kleinjans JCS
- Issue date: 2017 Jun
- Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water.
- Authors: Moffat I, Chepelev N, Labib S, Bourdon-Lacombe J, Kuo B, Buick JK, Lemieux F, Williams A, Halappanavar S, Malik A, Luijten M, Aubrecht J, Hyduke DR, Fornace AJ Jr, Swartz CD, Recio L, Yauk CL
- Issue date: 2015 Jan
- Parallelogram approach using rat-human in vitro and rat in vivo toxicogenomics predicts acetaminophen-induced hepatotoxicity in humans.
- Authors: Kienhuis AS, van de Poll MC, Wortelboer H, van Herwijnen M, Gottschalk R, Dejong CH, Boorsma A, Paules RS, Kleinjans JC, Stierum RH, van Delft JH
- Issue date: 2009 Feb