Dietary fish oil reduces O6-methylguanine DNA adduct levels in rat colon in part by increasing apoptosis during tumor initiation.
dc.contributor.author | Hong, Mee Y | |
dc.contributor.author | Lupton, Joanne R | |
dc.contributor.author | Morris, Jeffrey S | |
dc.contributor.author | Wang, Naisyin | |
dc.contributor.author | Carroll, Raymond J | |
dc.contributor.author | Davidson, Laurie A | |
dc.contributor.author | Elder, Rhoderick H | |
dc.contributor.author | Chapkin, Robert S | |
dc.date.accessioned | 2009-12-29T10:22:10Z | |
dc.date.available | 2009-12-29T10:22:10Z | |
dc.date.issued | 2000-08 | |
dc.identifier.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. | en |
dc.identifier.issn | 1055-9965 | |
dc.identifier.pmid | 10952099 | |
dc.identifier.uri | http://hdl.handle.net/10541/88615 | |
dc.description.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. | |
dc.language.iso | en | en |
dc.subject | Colon Cancer | en |
dc.subject.mesh | Analysis of Variance | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Anticarcinogenic Agents | |
dc.subject.mesh | Apoptosis | |
dc.subject.mesh | Colonic Neoplasms | |
dc.subject.mesh | DNA Adducts | |
dc.subject.mesh | DNA Damage | |
dc.subject.mesh | DNA Repair | |
dc.subject.mesh | Fish Oils | |
dc.subject.mesh | Guanine | |
dc.subject.mesh | Intestinal Mucosa | |
dc.subject.mesh | Likelihood Functions | |
dc.subject.mesh | Male | |
dc.subject.mesh | Rats | |
dc.subject.mesh | Rats, Sprague-Dawley | |
dc.subject.mesh | Statistics, Nonparametric | |
dc.subject.mesh | tRNA Methyltransferases | |
dc.title | Dietary fish oil reduces O6-methylguanine DNA adduct levels in rat colon in part by increasing apoptosis during tumor initiation. | en |
dc.type | Article | en |
dc.contributor.department | Molecular and Cell Biology Section, Faculty of Nutrition, Texas A&M University, College Station 77843-2471, USA. | en |
dc.identifier.journal | Cancer Epidemiology, Biomarkers & Prevention | en |
html.description.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. |