This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hong, M. Y. Articles by Chapkin, R. S. Search for Related Content PubMed PubMed Citation Articles by Hong, M. Y. Articles by Chapkin, R. S.

Dietary Fish Oil Reduces O⁶-Methylguanine DNA Adduct Levels in Rat Colon in Part by Increasing Apoptosis during Tumor Initiation¹

Molecular and Cell Biology Section, Faculty of Nutrition [M. Y. H., J. R. L., R. J. C., L. A. D., R. S. C.], Department of Statistics [J. S. M., N. W., R. J. C.], and Center for Environmental and Rural Health [J. R. L., N. W., R. J. C., R. S. C.], Texas A&M University, College Station, Texas 77843-2471, and Paterson Institute for Cancer Research, Manchester, M20 4BX United Kingdom [R. H. E.]

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.

This article has been cited by other articles:

				Y. Hu, G. H. McIntosh, R. K. Le Leu, R. Woodman, and G. P. Young Suppression of Colorectal Oncogenesis by Selenium-Enriched Milk Proteins: Apoptosis and K-ras Mutations Cancer Res., June 15, 2008; 68(12): 4936 - 4944. [Abstract] [Full Text] [PDF]

				Q. Jia, J. R. Lupton, R. Smith, B. R. Weeks, E. Callaway, L. A. Davidson, W. Kim, Y.-Y. Fan, P. Yang, R. A. Newman, et al. Reduced Colitis-Associated Colon Cancer in Fat-1 (n-3 Fatty Acid Desaturase) Transgenic Mice Cancer Res., May 15, 2008; 68(10): 3985 - 3991. [Abstract] [Full Text] [PDF]

				S. S. N. Kolar, R. Barhoumi, E. S. Callaway, Y.-Y. Fan, N. Wang, J. R. Lupton, and R. S. Chapkin Synergy between docosahexaenoic acid and butyrate elicits p53-independent apoptosis via mitochondrial Ca2+ accumulation in colonocytes Am J Physiol Gastrointest Liver Physiol, November 1, 2007; 293(5): G935 - G943. [Abstract] [Full Text] [PDF]

				S. S. N. Kolar, R. Barhoumi, J. R. Lupton, and R. S. Chapkin Docosahexaenoic Acid and Butyrate Synergistically Induce Colonocyte Apoptosis by Enhancing Mitochondrial Ca2+ Accumulation Cancer Res., June 1, 2007; 67(11): 5561 - 5568. [Abstract] [Full Text] [PDF]

				Y. Ng, R. Barhoumi, R. B. Tjalkens, Y.-Y. Fan, S. Kolar, N. Wang, J. R. Lupton, and R. S. Chapkin The role of docosahexaenoic acid in mediating mitochondrial membrane lipid oxidation and apoptosis in colonocytes Carcinogenesis, November 1, 2005; 26(11): 1914 - 1921. [Abstract] [Full Text] [PDF]

				B. S. Reddy, J. M. Patlolla, B. Simi, S.H. Wang, and C. V. Rao Prevention of Colon Cancer by Low Doses of Celecoxib, a Cyclooxygenase Inhibitor, Administered in Diet Rich in {omega}-3 Polyunsaturated Fatty Acids Cancer Res., September 1, 2005; 65(17): 8022 - 8027. [Abstract] [Full Text] [PDF]

				G.-D. Zhou, N. Popovic, J. R. Lupton, N. D. Turner, R. S. Chapkin, and K. C. Donnelly Tissue-Specific Attenuation of Endogenous DNA I-Compounds in Rats by Carcinogen Azoxymethane: Possible Role of Dietary Fish Oil in Colon Cancer Prevention Cancer Epidemiol. Biomarkers Prev., May 1, 2005; 14(5): 1230 - 1235. [Abstract] [Full Text] [PDF]

				B. A. Narayanan, N. K. Narayanan, D. Desai, B. Pittman, and B. S. Reddy Effects of a combination of docosahexaenoic acid and 1,4-phenylene bis(methylene) selenocyanate on cyclooxygenase 2, inducible nitric oxide synthase and {beta}-catenin pathways in colon cancer cells Carcinogenesis, December 1, 2004; 25(12): 2443 - 2449. [Abstract] [Full Text] [PDF]

				L. M. Sanders, C. E. Henderson, M. Y. Hong, R. Barhoumi, R. C. Burghardt, N. Wang, C. M. Spinka, R. J. Carroll, N. D. Turner, R. S. Chapkin, et al. An Increase in Reactive Oxygen Species by Dietary Fish Oil Coupled with the Attenuation of Antioxidant Defenses by Dietary Pectin Enhances Rat Colonocyte Apoptosis J. Nutr., December 1, 2004; 134(12): 3233 - 3238. [Abstract] [Full Text] [PDF]

				M. Brink, M. P. Weijenberg, A. F. P. M. de Goeij, L. J. Schouten, F. D. H. Koedijk, G. M. J. M. Roemen, M. H. F. M. Lentjes, A. P. de Bruine, R.A. Goldbohm, and P. A. van den Brandt Fat and K-ras mutations in sporadic colorectal cancer in The Netherlands Cohort Study Carcinogenesis, September 1, 2004; 25(9): 1619 - 1628. [Abstract] [Full Text] [PDF]

				M. V. Swamy, I. Cooma, J. M.R. Patlolla, B. Simi, B. S. Reddy, and C. V. Rao Modulation of cyclooxygenase-2 activities by the combined action of celecoxib and decosahexaenoic acid: Novel strategies for colon cancer prevention and treatment Mol. Cancer Ther., February 1, 2004; 3(2): 215 - 221. [Abstract] [Full Text] [PDF]

				J. R. Lupton Microbial Degradation Products Influence Colon Cancer Risk: the Butyrate Controversy J. Nutr., February 1, 2004; 134(2): 479 - 482. [Abstract] [Full Text] [PDF]

				Y.-Y. Fan, T. E. Spencer, N. Wang, M. P. Moyer, and R. S. Chapkin Chemopreventive n-3 fatty acids activate RXR{alpha} in colonocytes Carcinogenesis, September 1, 2003; 24(9): 1541 - 1548. [Abstract] [Full Text] [PDF]

				M. Y. Hong, R. S. Chapkin, R. Barhoumi, R. C. Burghardt, N. D. Turner, C. E. Henderson, L. M. Sanders, Y.-Y. Fan, L. A. Davidson, M. E. Murphy, et al. Fish oil increases mitochondrial phospholipid unsaturation, upregulating reactive oxygen species and apoptosis in rat colonocytes Carcinogenesis, November 1, 2002; 23(11): 1919 - 1926. [Abstract] [Full Text] [PDF]

				E. I. Salim, H. Wanibuchi, K. Morimura, T. Murai, S. Makino, T. Nomura, and S. Fukushima Induction of tumors in the colon and liver of the immunodeficient (SCID) mouse by 2-amino-3-methylimidazo[4,5-f ]quinoline (IQ)--modulation by long-chain fatty acids Carcinogenesis, September 1, 2002; 23(9): 1519 - 1529. [Abstract] [Full Text] [PDF]

				E. D. Collett, L. A. Davidson, Y.-Y. Fan, J. R. Lupton, and R. S. Chapkin n-6 and n-3 polyunsaturated fatty acids differentially modulate oncogenic Ras activation in colonocytes Am J Physiol Cell Physiol, May 1, 2001; 280(5): C1066 - C1075. [Abstract] [Full Text] [PDF]