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dc.contributor.authorHong, Mee Y
dc.contributor.authorLupton, Joanne R
dc.contributor.authorMorris, Jeffrey S
dc.contributor.authorWang, Naisyin
dc.contributor.authorCarroll, Raymond J
dc.contributor.authorDavidson, Laurie A
dc.contributor.authorElder, Rhoderick H
dc.contributor.authorChapkin, Robert S
dc.date.accessioned2009-12-29T10:22:10Z
dc.date.available2009-12-29T10:22:10Z
dc.date.issued2000-08
dc.identifier.citationDietary 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.en
dc.identifier.issn1055-9965
dc.identifier.pmid10952099
dc.identifier.urihttp://hdl.handle.net/10541/88615
dc.description.abstractThere 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.
dc.language.isoenen
dc.subjectColon Canceren
dc.subject.meshAnalysis of Variance
dc.subject.meshAnimals
dc.subject.meshAnticarcinogenic Agents
dc.subject.meshApoptosis
dc.subject.meshColonic Neoplasms
dc.subject.meshDNA Adducts
dc.subject.meshDNA Damage
dc.subject.meshDNA Repair
dc.subject.meshFish Oils
dc.subject.meshGuanine
dc.subject.meshIntestinal Mucosa
dc.subject.meshLikelihood Functions
dc.subject.meshMale
dc.subject.meshRats
dc.subject.meshRats, Sprague-Dawley
dc.subject.meshStatistics, Nonparametric
dc.subject.meshtRNA Methyltransferases
dc.titleDietary fish oil reduces O6-methylguanine DNA adduct levels in rat colon in part by increasing apoptosis during tumor initiation.en
dc.typeArticleen
dc.contributor.departmentMolecular and Cell Biology Section, Faculty of Nutrition, Texas A&M University, College Station 77843-2471, USA.en
dc.identifier.journalCancer Epidemiology, Biomarkers & Preventionen
html.description.abstractThere 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.


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