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    Effects of Schistosoma haematobium infection on drug-metabolizing enzymes in human bladder cancer tissues.

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    Authors
    Sheweita, S A
    El-Shahat, F G
    Bazeed, M A
    Abu El-Maati, M R
    O'Connor, Peter J
    Affiliation
    Department of Bioscience and Technology, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt. sheweita@hotmail.com
    Issue Date
    2004-03-08
    
    Metadata
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    Abstract
    The mixed function oxidase system includes the phase I drug oxidation proteins e.g. aryl hydrocarbon hydroxylase (AHH), N-nitrosodimethylamine-N-demethylase I (NDMA-dI) and cytochrome b5 which metabolize most carcinogens and xenobiotics into less and/or more active intermediates. These were determined in human bladder tissues diagnosed as bladder cancer only (10 samples) and bladder cancer associated with Schistosoma haematobium (12 samples) and normal bladder tissues (12 samples). In addition to the above enzymes, agents involved in Phase II drug metabolism e.g. glutathione and glutathione S-transferase as well as free radicals (detected as thiobarbituric acid-reactive substances, TBARS) were also determined in these tissues samples. AAH and NDMA-dI, cytochrome b5, and glutathione S-transferase activity decreased by 42, 28, 47 and 32%, respectively, in human bladder cancer tissues. In bladder cancer tissues associated with S. haematobium infection NDMA-dI and GST activity decreased further by 65 and 56%, respectively, whereas AHH activity increased by 50% and levels of reduced glutathione also increased by 43% in cancer tissue and by 29% in schistocome infected bladder cancer tissue. The level of free radicals also increased significantly (by 57%) in infected bladder cancer tissue but not at all in non-infected cancer tissue. Alterations in the activity of phase I and II of drug-metabolizing enzymes in human bladder tissues as a result of S. haematobium infection may therefore change the bladder's capacity to detoxify many endogenous compounds and may also potentiate the deleterious effects of bladder carcinogens, (e.g. N-nitrosamines) which are known to be present in relatively large quantities in the bladder of patients with schistosomiasis. The present study thus provides new insights into mechanisms for the genesis of bladder cancer initiated in association with schistosomiasis.
    Citation
    Effects of Schistosoma haematobium infection on drug-metabolizing enzymes in human bladder cancer tissues. 2004, 205 (1):15-21 Cancer Lett.
    Journal
    Cancer Letters
    URI
    http://hdl.handle.net/10541/78175
    DOI
    10.1016/j.canlet.2003.09.023
    PubMed ID
    15036656
    Type
    Article
    Language
    en
    ISSN
    0304-3835
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.canlet.2003.09.023
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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