• Login
    View Item 
    •   Repository
    • Open Access Articles
    • Open Access Journals
    • Biology and Biotechnology
    • View Item
    •   Repository
    • Open Access Articles
    • Open Access Journals
    • Biology and Biotechnology
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    N–nitrosodiethylamine cytochrome P450 induction and cytotoxicity evaluation in primary cultures of rat hepatocytes

    Thumbnail
    View/Open
    Full text (392.2Kb)
    Date
    2011-07
    Author
    Aiub, Claudia A.
    Gadermaier, Gabriele
    Ferreira, Fátima
    Felzenszwalb, Israel
    Eckl, Peter
    Pinto, Luis F.
    Metadata
    Show full item record
    Abstract
    The primary routes of potential human exposure to N-nitrosodiethylamine (NDEA) are ingestion, inhalation, and dermal contact. Air, diet and smoking contribute to potential human exposure at levels of a few µg of NDEA/day. Potential exposure depends on the ability of the nitrosamines to migrate from the product into the body. The first step in the metabolic degradation of NDEA by cytochrome oxidase (CYPs) enzymes is the introduction of a hydroxyl group and in human esophage and liver CYP2A3 and CYP2E1 participate on this metabolism. Measuring cytotoxicity in female rat primary hepatocytes cultures, were used to understand the CYP induction and metaboli-zation correlated with low NDEA concentrations. We observed that NDEA at different concentrations in the absence of CYPs inducers, was able to induce CYP2B1, CYP2B2, CYP2E1, CYP3A1 and CYP4A3. A positive NDEA synergistic effect on the levels of mRNA, was observed in the presence of pyrazole (300 µM) for CYP2B1 and CYP2B2 and for pregnenolone 16- carbonitrile (0.15 µM) for CYP2E1. Negative NDEA synergistic effects were observed for ethanol (0.3%) for CYP3A1, pyrazol (300 µM) for CYP2A1 and CYP2E1, and phenobarbital (1 mM) for CYP2A1. These facts are extremally important once that these metabolites can be directly related to the primary DNA lesions. We consider that studies to elucidate the biological factors that determine the shape of the dose-response curve are crucial for low-dose extrapolations of risk.
    URI
    http://dx.doi.org/10.4236/ajmb.2011.12009
    http://hdl.handle.net/123456789/969
    Collections
    • Biology and Biotechnology [193]

    University of Embu©
    Contact Us |
    Designed by 
    Atmire NV
     

     

    Browse

    All of RepositoryCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    University of Embu©
    Contact Us |
    Designed by 
    Atmire NV