ArticleEnvironmental health perspectives2016
Using ToxCast™ Data to Reconstruct Dynamic Cell State Trajectories and Estimate Toxicological Points of Departure.
Article in Environmental health perspectives, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43 citing papers in PubMed.
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- Decoding Cellular Stress States for Toxicology Using Single-Cell Transcriptomics.bioRxiv : the preprint server for biology · 2025Article
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- Assessment of Drug-Induced Liver Injury through Cell Morphology and Gene Expression Analysis.Chemical research in toxicology · 2023Article
- Early microRNA responses in rodent liver mediated by furan exposure establish dose thresholds for later adverse outcomes.Toxicology letters · 2023Article
- Development of a reference and proficiency chemical list for human steatosis endpointsFrontiers in endocrinology · 2023Review
- Using high throughput screens to predict miscarriages with placental stem cells and long-term stress effects with embryonic stem cells.Birth defects research · 2022Review
- Integrating cell morphology with gene expression and chemical structure to aid mitochondrial toxicity detection.Communications biology · 2022Article
- Integrated Omic Analyses Identify Pathways and Transcriptomic Regulators Associated With Chemical Alterations of In Vitro Neural Network Formation.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Mapping the cellular response to electron transport chain inhibitors reveals selective signaling networks triggered by mitochondrial perturbation.Archives of toxicology · 2022Article
- Altered network and rescue of human neurons derived from individuals with early-onset genetic epilepsy.Molecular psychiatry · 2021Article
- Evaluating adaptive stress response gene signatures using transcriptomics.Computational toxicology (Amsterdam, Netherlands) · 2021Article
- Estimating Hepatotoxic Doses Using High-Content Imaging in Primary Hepatocytes.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Using Live Imaging and FUCCI Embryonic Stem Cells to Rank DevTox Risks: Adverse Growth Effects of PFOA Compared With DEP Are 26 Times Faster, 1,000 Times More Sensitive, and 13 Times Greater in Magnitude.Frontiers in toxicology · 2021Article
- Chlorpyrifos and ΔCurrent research in toxicology · 2021Review
- A set of six Gene expression biomarkers and their thresholds identify rat liver tumorigens in short-term assays.Toxicology · 2020Article
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14 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundHigh-content imaging (HCI) allows simultaneous measurement of multiple cellular phenotypic changes and is an important tool for evaluating the biological activity of chemicals.
objectivesOur goal was to analyze dynamic cellular changes using HCI to identify the "tipping point" at which the cells did not show recovery towards a normal phenotypic state.
methodsHCI was used to evaluate the effects of 967 chemicals (in concentrations ranging from 0.4 to 200 μM) on HepG2 cells over a 72-hr exposure period. The HCI end points included p53, c-Jun, histone H2A.x, α-tubulin, histone H3, alpha tubulin, mitochondrial membrane potential, mitochondrial mass, cell cycle arrest, nuclear size, and cell number. A computational model was developed to interpret HCI responses as cell-state trajectories.
resultsAnalysis of cell-state trajectories showed that 336 chemicals produced tipping points and that HepG2 cells were resilient to the effects of 334 chemicals up to the highest concentration (200 μM) and duration (72 hr) tested. Tipping points were identified as concentration-dependent transitions in system recovery, and the corresponding critical concentrations were generally between 5 and 15 times (25th and 75th percentiles, respectively) lower than the concentration that produced any significant effect on HepG2 cells. The remaining 297 chemicals require more data before they can be placed in either of these categories.
conclusionsThese findings show the utility of HCI data for reconstructing cell state trajectories and provide insight into the adaptation and resilience of in vitro cellular systems based on tipping points. Cellular tipping points could be used to define a point of departure for risk-based prioritization of environmental chemicals. CITATION: Shah I, Setzer RW, Jack J, Houck KA, Judson RS, Knudsen TB, Liu J, Martin MT, Reif DM, Richard AM, Thomas RS, Crofton KM, Dix DJ, Kavlock RJ. 2016. Using ToxCast™ data to reconstruct dynamic cell state trajectories and estimate toxicological points of departure. Environ Health Perspect 124:910-919; http://dx.doi.org/10.1289/ehp.1409029.
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