ArticleToxicology2025
Assessing the impact of in vitro xenobiotic metabolism on estrogenic chemical bioactivity in high-throughput profiling assays.
Article in Toxicology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
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9 authors.
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Abstract
High-throughput profiling assays such as high-throughput phenotypic profiling (HTPP) with Cell Painting and high-throughput transcriptomics (HTTr) are new approach methods that have been used to characterize the bioactivity and potential hazards of chemicals. To enhance the ability to identify potential in vivo hazards during chemical screening, we previously coupled both assays to an in vitro metabolism platform, Alginate Immobilization of Metabolic Enzymes (AIME). In this study, we used the AIME platform to expand upon our previous results for three estrogenic reference chemicals by screening an additional 40 chemicals anticipated to have varied activity and/or shifts in activity with metabolism in an estrogen receptor transactivation assay (ERTA) in VM7Luc4E2 breast carcinoma cells. The results demonstrated that HTTr could detect estrogen receptor (ER) activation and identify chemicals with metabolism-induced shifts in estrogenicity via ER gene signature enrichment analysis. Additionally, HTPP could detect cases where metabolism impacted chemical cytotoxicity and cases where metabolites generated by AIME produced distinct bioactivity profiles compared to their respective parent compounds. Notably, our findings highlighted examples of chemicals that had very different phenotypic and gene expression profiles between metabolic conditions that would not be observed in traditional chemical screening in most immortalized cell line models. Incorporation of metabolism using the AIME platform into high-throughput profiling assays could help inform next generation risk assessment by providing more comprehensive hazard characterizations.
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