ArticlePloS one2017
Establishment of a novel hepatocyte model that expresses four cytochrome P450 genes stably via mammalian-derived artificial chromosome for pharmacokinetics and toxicity studies.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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
13 citing papers in PubMed, 20 citations in OpenAlex.
- Drug-Metabolizing Gene Expression Identity: Comparison Across Liver Tissues and Model Cell Lines.Biomedicines · 2025Article
- Mono-CYP CHO Model: A Recombinant Chinese Hamster Ovary Cell Platform for Investigating CYP-Specific Tamoxifen Metabolism.International journal of molecular sciences · 2025Article
- Combination of melt-electrospun poly-ε-caprolactone scaffolds and hepatocyte-like cells from footprint-free hiPSCs to create 3D biohybrid constructs for liver tissue engineering.Scientific reports · 2023Article
- Article
- Investigation of Radiotracer Metabolic Stability In Vitro with CYP-Overexpressing Hepatoma Cell Lines.Cells · 2022Article
- Article
- Functional expression and regulation of eukaryotic cytochrome P450 enzymes in surrogate microbial cell factories.Engineering microbiology · 2022Review
- Construction of stable mouse artificial chromosome from native mouse chromosome 10 for generation of transchromosomic mice.Scientific reports · 2021Article
- Bioluminescence Measurement of Time-Dependent Dynamic Changes of CYP-Mediated Cytotoxicity in CYP-Expressing Luminescent HepG2 Cells.International journal of molecular sciences · 2021Article
- Development of Caco-2 cells expressing four CYPs via a mammalian artificial chromosome.BMC biotechnology · 2020Article
- The Multifarious Link between Cytochrome P450s and Cancer.Oxidative medicine and cellular longevity · 2020Review
- Humanized UGT2 and CYP3A transchromosomic rats for improved prediction of human drug metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Current High-Throughput Approaches of Screening Modulatory Effects of Xenobiotics on Cytochrome P450 (CYP) Enzymes.High-throughput · 2018Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The utility of HepG2 cells to assess drug metabolism and toxicity induced by chemical compounds is hampered by their low cytochrome P450 (CYP) activities. To overcome this limitation, we established HepG2 cell lines expressing major CYP enzymes involved in drug metabolism (CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and CYP oxidoreductase (POR) using the mammalian-derived artificial chromosome vector. Transchromosomic HepG2 (TC-HepG2) cells expressing four CYPs and POR were used to determine time- and concentration-dependent inhibition and toxicity of several compounds by luminescence detection of CYP-specific substrates and cell viability assays. Gene expression levels of all four CYPs and POR, as well as the CYP activities, were higher in TC-HepG2 clones than in parental HepG2 cells. Additionally, the activity levels of all CYPs were reduced in a concentration-dependent manner by specific CYP inhibitors. Furthermore, preincubation of TC-HepG2 cells with CYP inhibitors known as time-dependent inhibitors (TDI) prior to the addition of CYP-specific substrates determined that CYP inhibition was enhanced in the TDI group than in the non-TDI group. Finally, the IC50 of bioactivable compound aflatoxin B1 was lower in TC-HepG2 cells than in HepG2 cells. In conclusion, the TC-HepG2 cells characterized in the current study are a highly versatile model to evaluate drug-drug interactions and hepatotoxicity in initial screening of candidate drug compounds, which require a high degree of processing capacity and reliability.
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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.