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    Dietary fish oil reduces O6-methylguanine DNA adduct levels in rat colon in part by increasing apoptosis during tumor initiation.

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    Authors
    Hong, Mee Y
    Lupton, Joanne R
    Morris, Jeffrey S
    Wang, Naisyin
    Carroll, Raymond J
    Davidson, Laurie A
    Elder, Rhoderick H
    Chapkin, Robert S
    Affiliation
    Molecular and Cell Biology Section, Faculty of Nutrition, Texas A&M University, College Station 77843-2471, USA.
    Issue Date
    2000-08
    
    Metadata
    Show full item record
    Abstract
    There is epidemiological, clinical, and experimental evidence that dietary fish oil, containing n-3 polyunsaturated fatty acids, protects against colon tumor development. However, its effects on colonocytes in vivo remain poorly understood. Therefore, we investigated the ability of fish oil to modulate colonic methylation-induced DNA damage, repair, and deletion. Sprague Dawley rats were provided with complete diets containing either corn oil or fish oil (15% by weight). Animals were injected with azoxymethane, and the distal colon was removed 3, 6, 9, or 12 h later. Targeted apoptosis and DNA damage were assessed by cell position within the crypt using the terminal deoxynucleotidyl transferase-mediated nick end labeling assay and quantitative immunohistochemical analysis of O6-methylguanine adducts, respectively. Localization and expression of the alkyl group acceptor, O6-methylguanine-DNA-methyltransferase, was also determined. Lower levels of adducts were detected at 6, 9, and 12 h in fish oil- versus corn oil-fed animals (P < 0.05). In addition, fish oil supplementation had the greatest effect on apoptosis in the top one-third of the crypt, increasing the apoptotic index compared with corn oil-fed rats (P < 0.05). In the top one-third of the crypt, fish oil feeding caused an incremental stimulation of apoptosis as adduct level increased. In contrast, a negative correlation between apoptosis and adduct incidence occurred with corn oil feeding (P < 0.05). Diet had no main effect (all tertiles combined) on O6-methylguanine-DNA-methyltransferase expression over the time frame of the experiment. The enhancement of targeted apoptosis combined with the reduced formation of O6-methylguanine adducts may account, in part, for the observed protective effect of n-3 polyunsaturated fatty acids against experimentally induced colon cancer.
    Citation
    Dietary fish oil reduces O6-methylguanine DNA adduct levels in rat colon in part by increasing apoptosis during tumor initiation. 2000, 9 (8):819-26 Cancer Epidemiol. Biomarkers Prev.
    Journal
    Cancer Epidemiology, Biomarkers & Prevention
    URI
    http://hdl.handle.net/10541/88615
    PubMed ID
    10952099
    Type
    Article
    Language
    en
    ISSN
    1055-9965
    Collections
    All Paterson Institute for Cancer Research

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