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

2.50
Hdl Handle:
http://hdl.handle.net/10541/88615
Title:
Dietary fish oil reduces O6-methylguanine DNA adduct levels in rat colon in part by increasing apoptosis during tumor initiation.
Authors:
Hong, Mee Y; Lupton, Joanne R; Morris, Jeffrey S; Wang, Naisyin; Carroll, Raymond J; Davidson, Laurie A; Elder, Rhoderick H; Chapkin, Robert S
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.
Affiliation:
Molecular and Cell Biology Section, Faculty of Nutrition, Texas A&M University, College Station 77843-2471, USA.
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
Issue Date:
Aug-2000
URI:
http://hdl.handle.net/10541/88615
PubMed ID:
10952099
Type:
Article
Language:
en
ISSN:
1055-9965
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorHong, Mee Yen
dc.contributor.authorLupton, Joanne Ren
dc.contributor.authorMorris, Jeffrey Sen
dc.contributor.authorWang, Naisyinen
dc.contributor.authorCarroll, Raymond Jen
dc.contributor.authorDavidson, Laurie Aen
dc.contributor.authorElder, Rhoderick Hen
dc.contributor.authorChapkin, Robert Sen
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.en
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

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