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    The Presence of Inducible Cytochrome P450 Types 1A1 and 1A2 in the BeWo Cell Line

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    Audus_AFD_Avery et al Placenta 2003.pdf (266.6Kb)
    Issue Date
    2003
    Author
    Avery, Michael
    Meek, C. E.
    Audus, Kenneth L.
    Publisher
    Elsevier
    Type
    Article
    Article Version
    Scholarly/refereed, author accepted manuscript
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    Abstract
    The activity and inducibility of cytochrome P450 systems (CYP1A1:1A2) of the human placenta were assessed in a representative human trophoblast-like cell line, BeWo. The activity of CYP1A1 and CYP1A2 in microsome preparations from human liver, placenta, primary cultures of human cytotrophoblast, and BeWo cells was measured by O-dealkylation of 7-ethoxyresorufin (EROD) and 7-methoxyresorufin O-demethylation (MROD), respectively. Results indicated high EROD and MROD activity associated with human liver microsomes, sometimes comparable activities in human placenta microsomes prepared from smokers, and relatively low activities in human placenta microsomes from nonsmokers and in the primary cultures of cytotrophoblasts isolated from nonsmokers. Microsomes from BeWo cell monolayers exhibited the lowest EROD and MROD activities relative to all other microsome preparations. However, compared to primary cultures of normal trophoblasts, the EROD activity of the BeWo cells was far more sensitive to typical inducers, 3-methylcholanthrene, 1,2-benzanthracene, and β-naphthoflavone. EROD activity in BeWo cells was induced approximately 200-fold by 3-methylcholanthrene. Both EROD and MROD activity in BeWo cells was readily induced by 1,2-benzanthracene, 100-fold and 60-fold, respectively. After induction with 1,2-benzanthracene, the CYP1A1 selective inhibitor, α-naphthoflavone, and the CYP1A2 selective inhibitor, furafylline, effectively inhibited enzyme activities with IC50’s of 2.4μM and 12.8μM, respectively, in microsomes from both trophoblasts culture systems. These results show that major cytochrome P450 forms present in human placenta are present and inducible in BeWo cells, a potential model for investigation of drug metabolism mechanisms in the human trophoblast.
    Description
    Please note that this is an author-produced PDF of an article accepted for publication following peer review. The publisher version is available on its site.
    URI
    http://hdl.handle.net/1808/7484
    DOI
    https://doi.org/10.1053/plac.2002.0876
    Collections
    • Pharmacy Scholarly Works [286]
    Citation
    Avery, M.L., Meek, C.E., and Audus, K.L. (2003) The presence of inducible cytochrome P450 types 1A1 and 1A2 in the BeWo cell line. Placenta 24, 45-52. PMID: 12495659 http://dx.doi.org/10.1053/plac.2002.0876

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    KU Libraries
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    785-864-8983

    KU Libraries
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    Lawrence, KS 66045
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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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