ArticleToxicology in vitro : an international journal published in association with BIBRA2021
Exploration of xenobiotic metabolism within cell lines used for Tox21 chemical screening.
Article in Toxicology in vitro : an international journal published in association with BIBRA, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Reconstructing Liver Fibrosis: 3D Human Models, Microbiome Interfaces, and Therapeutic Innovation.Current issues in molecular biology · 2026Review
- On the Utilization and Characterization of External Biotransformation Systems inACS environmental Au · 2026Review
- Rapid behavioral screening in the planarianFrontiers in toxicology · 2026Article
- Design, synthesis and biological activity of glycoconjugated ADAMTS5 exosite inhibitors: applications in osteoarthritis and ovarian cancer models.Scientific reports · 2025Article
- Functional Liver Cell-Based Platforms in Biomedical Research.Pharmacology research & perspectives · 2025Review
- Application of cytochrome P450 enzyme assays to predict p53 inducers and AChE inhibitors that require metabolic activation.Toxicology and applied pharmacology · 2025Article
- In Vitro Metabolism and p53 Activation of Genotoxic Chemicals: Abiotic CYP Enzyme vs Liver Microsomes.Chemical research in toxicology · 2024Article
- Effects of Chemicals in Reporter Gene Bioassays with Different Metabolic Activities Compared to Baseline Toxicity.Chemical research in toxicology · 2024Article
- Reactivity of Acrylamides Causes Cytotoxicity and Activates Oxidative Stress Response.Chemical research in toxicology · 2023Article
- Umbelliferon: a review of its pharmacology, toxicity and pharmacokinetics.Inflammopharmacology · 2023Review
- Chronic PFOA exposure in vitro causes acquisition of multiple tumor cell characteristics in rat liver cells.Toxicology in vitro : an international journal published in association with BIBRA · 2023Article
- Using liver models generated from human-induced pluripotent stem cells (iPSCs) for evaluating chemical-induced modifications and disease across liver developmental stages.Toxicology in vitro : an international journal published in association with BIBRA · 2022Review
- StemPanTox: A fast and wide-target drug assessment system for tailor-made safety evaluations using personalized iPS cells.iScience · 2022Article
- Identification of environmental chemicals that activate p53 signaling after in vitro metabolic activation.Archives of toxicology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The Tox21 Program has investigated thousands of chemicals with high-throughput screening assays using cell-based assays to link thousands of chemicals to individual molecular targets/pathways. However, these systems have been widely criticized for their suspected lack of 'metabolic competence' to bioactivate or detoxify chemical exposures. In this study, 9 cell line backgrounds used in Tox21 assays (i.e., HepG2, HEK293, Hela, HCT116, ME180, CHO-K1, GH3.TRE-Luc, C3H10T1/2 and MCF7) were evaluated via metabolite formation rates, along with metabolic clearance and metabolite profiling for HepG2, HEK293, and MCF-7aroERE, in comparison to pooled donor (50) suspensions of primary human hepatocytes (PHHs). Using prototype clinical drug substrates for CYP1A2, CYP2B6, and CYP3A4/5, extremely low-to-undetectable CYP450 metabolism was observed (24 h), and consistent with their purported 'lack' of metabolic competence. However, for Phase II metabolizing enzymes and metabolic clearance, surprisingly proficient metabolism was observed for bisphenol AF, bisphenol S, and 7-hydroxycoumarin. Here, comparatively low glucuronidation relative to sulfation was observed in contrast to equivalent levels in PHHs. Overall, while a lack of CYP450 metabolism was confirmed in this benchmarking effort, Tox21 cell lines were not 'incompetent' for xenobiotic metabolism, and displayed surprisingly high proficiency for sulfation that rivaled PHHs. These findings have implications for the interpretation of Tox21 assay data, and establish a framework for evaluating of 'metabolic competence' with in vitro models.
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Registered trials
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.