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    Smoking is associated with a decrease of O6-alkylguanine-DNA alkyltransferase activity in bronchial epithelial cells.

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    Authors
    Povey, Andrew C
    O'Donnell, Paul
    Barber, Philip V
    Watson, Amanda J
    Margison, Geoffrey P
    Santibanez-Koref, Mauro F
    Affiliation
    Centre for Occupational and Environmental Health, University of Manchester, Manchester, United Kingdom. a.povey@manchester.ac.uk
    Issue Date
    2006-07-15
    
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    Abstract
    O6-alkylguanine-DNA alkyltransferase (MGMT) represents the first line of defense against the toxic, mutagenic and carcinogenic effects of O6-alkylguanine adducts in DNA. These adducts mediate the biological activity from a series of alkylating agents, such as the tobacco-specific nitrosamines, believed to contribute to the carcinogenicity of tobacco smoke. There have been conflicting reports on the effects of smoking on MGMT activity in lung and other tissues. Here, we investigate MGMT activity in peripheral blood mononuclear cells (PBMC) and lung bronchial epithelial cells (BEC), extracted by lung brushings, from smokers and nonsmokers attending a bronchoscopy clinic. MGMT activity was significantly lower in BECs (geometric mean; 95% confidence interval 1.02; 0.86-1.20 fmol/microg DNA) than in PBMCs (7.86; 6.70-9.59 fmol/microg DNA; p < 0.001), suggesting that bronchial epithelia may be particularly sensitive to alkylation damage. More importantly our results indicate that activity in BECs is significantly decreased in samples from current smokers (0.71; 0.54-0.93 fmol/microg DNA) compared to nonsmokers (1.25; 1.03-1.51 fmol/microg DNA; p = 0.002). This could represent an important contribution to the carcinogenicity of tobacco smoke.
    Citation
    Smoking is associated with a decrease of O6-alkylguanine-DNA alkyltransferase activity in bronchial epithelial cells. 2006, 119 (2):463-6 Int. J. Cancer
    Journal
    International Journal of Cancer.
    URI
    http://hdl.handle.net/10541/72686
    DOI
    10.1002/ijc.21790
    PubMed ID
    16477630
    Type
    Article
    Language
    en
    ISSN
    0020-7136
    ae974a485f413a2113503eed53cd6c53
    10.1002/ijc.21790
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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