ArticleEnvironmental and molecular mutagenesis2015
Integration of metabolic activation with a predictive toxicogenomics signature to classify genotoxic versus nongenotoxic chemicals in human TK6 cells.
Article in Environmental and molecular mutagenesis, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Review of Transcriptomic Biomarkers That Predict In Vitro Genotoxicity in Human Cell Lines.Environmental and molecular mutagenesis · 2025Review
- Outcome of IWGT workshop on transcriptomic biomarkers for genotoxicity: Key considerations for bioinformatics.Environmental and molecular mutagenesis · 2025Review
- TGx-DDI (toxicogenomic DNA damage-inducing) biomarker validation: multi-site ring trial supporting regulatory use.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- A novel support vector machine-based 1-day, single-dose prediction model of genotoxic hepatocarcinogenicity in rats.Archives of toxicology · 2024Article
- Application of HepaRG cells for genotoxicity assessment: a review.Journal of environmental science and health. Part C, Toxicology and carcinogenesis · 2024Review
- Application of a new approach methodology (NAM)-based strategy for genotoxicity assessment of data-poor compounds.Frontiers in toxicology · 2023Article
- Review
- Comparative Analysis of Transcriptional Responses to Genotoxic and Non-Genotoxic Agents in the Blood Cell Model TK6 and the Liver Model HepaRG.International journal of molecular sciences · 2022Article
- CEBS update: curated toxicology database with enhanced tools for data integration.Nucleic acids research · 2022Article
- Integrated Genotoxicity Testing of three anti-infective drugs using the TGx-DDI transcriptomic biomarker and high-throughput CometChipFrontiers in toxicology · 2022Article
- A Modern Genotoxicity Testing Paradigm: Integration of the High-Throughput CometChip® and the TGx-DDI Transcriptomic Biomarker in Human HepaRG™ Cell Cultures.Frontiers in public health · 2021Article
- A cross-sector call to improve carcinogenicity risk assessment through use of genomic methodologies.Regulatory toxicology and pharmacology : RTP · 2020Article
- Flow cytometric micronucleus assay and TGx-DDI transcriptomic biomarker analysis of ten genotoxic and non-genotoxic chemicals in human HepaRG™ cells.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2020Article
- Multigene Biomarkers of Pyrethroid Exposure: Exploratory Experiments.Environmental toxicology and chemistry · 2019Article
- Identification of p53 Activators in a Human Microarray Compendium.Chemical research in toxicology · 2019Article
- Three-dimensional HepaRG spheroids as a liver model to study human genotoxicity in vitro with the single cell gel electrophoresis assay.Scientific reports · 2019Article
- The development and prevalidation of an in vitro mutagenicity assay based on MutaMouse primary hepatocytes, Part II: Assay performance for the identification of mutagenic chemicals.Environmental and molecular mutagenesis · 2019Article
- Assessment of the performance of the TGx-DDI biomarker to detect DNA damage-inducing agents using quantitative RT-PCR in TK6 cells.Environmental and molecular mutagenesis · 2019Article
- TGx-DDI, a Transcriptomic Biomarker for Genotoxicity Hazard Assessment of Pharmaceuticals and Environmental Chemicals.Frontiers in big data · 2019Review
- Using a gene expression biomarker to identify DNA damage-inducing agents in microarray profiles.Environmental and molecular mutagenesis · 2018Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
The use of integrated approaches in genetic toxicology, including the incorporation of gene expression data to determine the molecular pathways involved in the response, is becoming more common. In a companion article, a genomic biomarker was developed in human TK6 cells to classify chemicals as genotoxic or nongenotoxic. Because TK6 cells are not metabolically competent, we set out to broaden the utility of the biomarker for use with chemicals requiring metabolic activation. Specifically, chemical exposures were conducted in the presence of rat liver S9. The ability of the biomarker to classify genotoxic (benzo[a]pyrene, BaP; aflatoxin B1, AFB1) and nongenotoxic (dexamethasone, DEX; phenobarbital, PB) agents correctly was evaluated. Cells were exposed to increasing chemical concentrations for 4 hr and collected 0 hr, 4 hr, and 20 hr postexposure. Relative survival, apoptosis, and micronucleus frequency were measured at 24 hr. Transcriptome profiles were measured with Agilent microarrays. Statistical modeling and bioinformatics tools were applied to classify each chemical using the genomic biomarker. BaP and AFB1 were correctly classified as genotoxic at the mid- and high concentrations at all three time points, whereas DEX was correctly classified as nongenotoxic at all concentrations and time points. The high concentration of PB was misclassified at 24 hr, suggesting that cytotoxicity at later time points may cause misclassification. The data suggest that the use of S9 does not impair the ability of the biomarker to classify genotoxicity in TK6 cells. Finally, we demonstrate that the biomarker is also able to accurately classify genotoxicity using a publicly available dataset derived from human HepaRG cells.
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