ArticleEnvironmental and molecular mutagenesis2016
Application of the TGx-28.65 transcriptomic biomarker to classify genotoxic and non-genotoxic chemicals in human TK6 cells in the presence of rat liver S9.
Article in Environmental and molecular mutagenesis, 2016. 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- 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
- Consensus findings of an International Workshops on Genotoxicity Testing workshop on using transcriptomic biomarkers to predict genotoxicity.Environmental and molecular mutagenesis · 2025Review
- Outcome of IWGT workshop on transcriptomic biomarkers for genotoxicity: Key considerations for bioinformatics.Environmental and molecular mutagenesis · 2025Review
- Review of Transcriptomic Biomarkers That Predict In Vitro Genotoxicity in Human Cell Lines.Environmental and molecular mutagenesis · 2025Review
- Impacts of Inorganic Arsenic Exposure on Genetic Stability of Human Mesenchymal Stromal Cells.Journal of applied toxicology : JAT · 2025Article
- Deciphering per- and polyfluoroalkyl substances mode of action: comparative gene expression analysis in human liver spheroids.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Application of a new approach methodology (NAM)-based strategy for genotoxicity assessment of data-poor compounds.Frontiers in toxicology · 2023Article
- A Collaborative Initiative to Establish Genomic Biomarkers for Assessing Tumorigenic Potential to Reduce Reliance on Conventional Rodent Carcinogenicity Studies.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- 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
- Integrated Genotoxicity Testing of three anti-infective drugs using the TGx-DDI transcriptomic biomarker and high-throughput CometChipFrontiers in toxicology · 2022Article
- Commentary: Novel strategies and new tools to curtail the health effects of pesticides.Environmental health : a global access science source · 2021Article
- 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
- Mode of action-based risk assessment of genotoxic carcinogens.Archives of toxicology · 2020Review
- 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
- Identification of p53 Activators in a Human Microarray Compendium.Chemical research in toxicology · 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
- Considerations for Strategic Use of High-Throughput Transcriptomics Chemical Screening Data in Regulatory Decisions.Current opinion in toxicology · 2019Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
In vitro transcriptional signatures that predict toxicities can facilitate chemical screening. We previously developed a transcriptomic biomarker (known as TGx-28.65) for classifying agents as genotoxic (DNA damaging) and non-genotoxic in human lymphoblastoid TK6 cells. Because TK6 cells do not express cytochrome P450s, we confirmed accurate classification by the biomarker in cells co-exposed to 1% 5,6 benzoflavone/phenobarbital-induced rat liver S9 for metabolic activation. However, chemicals may require different types of S9 for activation. Here we investigated the response of TK6 cells to higher percentages of Aroclor-, benzoflavone/phenobarbital-, or ethanol-induced rat liver S9 to expand TGx-28.65 biomarker applicability. Transcriptional profiles were derived 3 to 4 hr following a 4 hr co-exposure of TK6 cells to test chemicals and S9. Preliminary studies established that 10% Aroclor- and 5% ethanol-induced S9 alone did not induce the TGx-28.65 biomarker genes. Seven genotoxic and two non-genotoxic chemicals (and concurrent solvent and positive controls) were then tested with one of the S9s (selected based on cell survival and micronucleus induction). Relative survival and micronucleus frequency was assessed by flow cytometry in cells 20 hr post-exposure. Genotoxic/non-genotoxic chemicals were accurately classified using the different S9s. One technical replicate of cells co-treated with dexamethasone and 10% Aroclor-induced S9 was falsely classified as genotoxic, suggesting caution in using high S9 concentrations. Even low concentrations of genotoxic chemicals (those not causing cytotoxicity) were correctly classified, demonstrating that TGx-28.65 is a sensitive biomarker of genotoxicity. A meta-analysis of datasets from 13 chemicals supports that different S9s can be used in TK6 cells, without impairing classification using the TGx-28.65 biomarker.
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Registered trials
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