ArticleArchives of toxicology2017
High-content imaging-based BAC-GFP toxicity pathway reporters to assess chemical adversity liabilities.
Article in Archives of toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 62 citations in OpenAlex.
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- A network-based transcriptomic landscape of HepG2 cells uncovering causal gene-cytotoxicity interactions underlying drug-induced liver injury.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Hepa-ToxMOA: a pathway-screening method for evaluating cellular stress and hepatic metabolic-dependent toxicity of natural products.Scientific reports · 2024Article
- Collaborative SAR Modeling and Prospective In Vitro Validation of Oxidative Stress Activation in Human HepG2 Cells.Journal of chemical information and modeling · 2023Article
- High-content high-throughput imaging reveals distinct connections between mitochondrial morphology and functionality for OXPHOS complex I, III, and V inhibitors.Cell biology and toxicology · 2023Article
- Stimulation of de novo glutathione synthesis by nitrofurantoin for enhanced resilience of hepatocytes.Cell biology and toxicology · 2022Article
- Model-based translation of DNA damage signaling dynamics across cell types.PLoS computational biology · 2022Article
- Dynamic modeling of Nrf2 pathway activation in liver cells after toxicant exposure.Scientific reports · 2022Article
- Towards an advanced testing strategy for genotoxicity using image-based 2D and 3D HepG2 DNA damage response fluorescent protein reporters.Mutagenesis · 2022Article
- Mapping the cellular response to electron transport chain inhibitors reveals selective signaling networks triggered by mitochondrial perturbation.Archives of toxicology · 2022Article
- HiPSC-Derived Hepatocyte-like Cells Can Be Used as a Model for Transcriptomics-Based Study of Chemical Toxicity.Toxics · 2021Article
- Fluorescent tagging of endogenous Heme oxygenase-1 in human induced pluripotent stem cells for high content imaging of oxidative stress in various differentiated lineages.Archives of toxicology · 2021Article
- The in vitro assessment of the toxicity of volatile, oxidisable, redox-cycling compounds: phenols as an example.Archives of toxicology · 2021Article
- Physiologically Relevant Estrogen Receptor Alpha Pathway Reporters for Single-Cell Imaging-Based Carcinogenic Hazard Assessment of Estrogenic Compounds.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Splicing factors control triple-negative breast cancer cell mitosis through SUN2 interaction and sororin intron retention.Journal of experimental & clinical cancer research : CR · 2021Article
- Effects of an Environmentally Relevant Mixture of Organophosphate Esters Derived From House Dust on Endochondral Ossification in Murine Limb Bud Cultures.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- High-Content Screening for the Detection of Drug-Induced Oxidative Stress in Liver Cells.Antioxidants (Basel, Switzerland) · 2021Review
- Dynamic Modeling of Mitochondrial Membrane Potential Upon Exposure to Mitochondrial Inhibitors.Frontiers in pharmacology · 2021Article
- Towards systems tissue engineering: Elucidating the dynamics, spatial coordination, and individual cells driving emergent behaviors.Biomaterials · 2020Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adaptive cellular stress responses are paramount in the healthy control of cell and tissue homeostasis and generally activated during toxicity in a chemical-specific manner. Here, we established a platform containing a panel of distinct adaptive stress response reporter cell lines based on BAC-transgenomics GFP tagging in HepG2 cells. Our current panel of eleven BAC-GFP HepG2 reporters together contains (1) upstream sensors, (2) downstream transcription factors and (3) their respective target genes, representing the oxidative stress response pathway (Keap1/Nrf2/Srxn1), the unfolded protein response in the endoplasmic reticulum (Xbp1/Atf4/BiP/Chop) and the DNA damage response (53bp1/p53/p21). Using automated confocal imaging and quantitative single-cell image analysis, we established that all reporters allowed the time-resolved, sensitive and mode-of-action-specific activation of the individual BAC-GFP reporter cell lines as defined by a panel of pathway-specific training compounds. Implementing the temporal pathway activity information increased the discrimination of training compounds. For a set of >30 hepatotoxicants, the induction of Srxn1, BiP, Chop and p21 BAC-GFP reporters correlated strongly with the transcriptional responses observed in cryopreserved primary human hepatocytes. Together, our data indicate that a phenotypic adaptive stress response profiling platform will allow a high throughput and time-resolved classification of chemical-induced stress responses, thus assisting in the future mechanism-based safety assessment of chemicals.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.