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Drug-Induced Liver Toxicity pp 151–177Cite as

Use of Liver-Derived Cell Lines for the Study of Drug-Induced Liver Injury

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Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

In vitro liver-derived cell lines have been used extensively in toxicity testing and related studies as alternatives and complements to primary hepatocytes. Multiple hepatocyte derived cellular carcinoma cell lines, such as HepG2, Huh7, and HepaRG cells, have been established over the years, and they display distinct characteristics regarding the expression and activity levels of drug-metabolizing enzymes and other hepatocyte-specific factors. These cell lines have become useful tools and the models based on cell lines showed promising value for screening risks of drug-induced liver injury (DILI) in the early stage of drug development, although they have deficiencies in metabolism-related investigations. Engineered cell lines, expressing drug-metabolizing enzymes or other hepatic genes either stably or transiently, have partially overcome these limitations. The liver-derived cell lines have contributed significantly to mechanistic studies of DILI, and various underlying signaling pathways and signatures of DILI have been identified. In this chapter, we first introduce the major hepatic lines (e.g., HepG2, Huh7, HepaRG, Hep3B, BC2, THLE, and Fa2N-4 cells), including their origins, characteristics, advantages, and disadvantages for application in toxicity studies. We next depict the development and application of various engineered cell lines. We then discuss the current understanding of major DILI mechanisms and the endpoints for in vitro tests. The chapter is closed with a brief discussion of the challenges and opportunities in the field.

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  1. Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA

    Zhen Ren, Si Chen & Lei Guo

  2. Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA

    Baitang Ning

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    Minjun Chen

  2. Drug Safety Research and Development, Pfizer Inc., Groton, CT, USA

    Yvonne Will

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Ren, Z., Chen, S., Ning, B., Guo, L. (2018). Use of Liver-Derived Cell Lines for the Study of Drug-Induced Liver Injury. In: Chen, M., Will, Y. (eds) Drug-Induced Liver Toxicity. Methods in Pharmacology and Toxicology. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-7677-5_8

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  • DOI: https://doi.org/10.1007/978-1-4939-7677-5_8

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-7676-8

  • Online ISBN: 978-1-4939-7677-5

  • eBook Packages: Springer Protocols

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