Dietary fish oil modulates the effect of dimethylhydrazine- induced colon cancer in rats

Authors

  • G. E. Rasmy Biochemistry Department, National Research Centre
  • W. K.B. Khalil Cell Biology Department, National Research Center
  • S. A. Moharib Biochemistry Department, National Research Centre
  • A. A. Kawkab Department of pathology- Faculty of Vet. Med. Cairo Univ.
  • E. W. Jwanny Biochemistry Department, National Research Centre

DOI:

https://doi.org/10.3989/gya.091210

Keywords:

Colorectal cancer, DMH, Fish oil, Gene expression, Rats

Abstract


This study was conducted to examine the efficacy of fish oil supplementation in male wistar rat colon carcinogenesis. In order to induce colon cancer, the rats were given a weekly subcutaneous injection of 1,2-Dimethylhydrazine (DMH) at a dose of 20 mg/kg b.w. for five weeks. Afterwards, some of the rats ingested fish oil for either 4 weeks (DMH-FO4 group), or 17 weeks (DMH-FO17 group). The remaining rats continued without any supplementation for the same 4 weeks (DMH4 group), or 17 weeks (DMH17 group). Another two groups of rats did not receive the DMH and were given fish oil (FO17 group) or a normal diet only and considered as the control group (CN group). At the end of the experiment, the rats were sacrificed; and were subsequently subjected to biochemical and molecular biological analyses as well as histopathological examinations. The results showed increased levels of lactate dehydrogenase (LDH), malondialdehyde (MDA) and alkaline phoshatase (ALP) activities in the DMH rats compared to the control. The liver and colonic changes that were induced by DMH were significantly improved through fish oil supplementation in the DMH-FO17 group. The molecular analysis revealed that DMH treatment induced the expression alterations of genes p53, p27 and p21 and increased DNA band patterns related to cancer, while both FO17 and DMH-FO17 groups showed much better results. A histopathological examination of the DMH17 group revealed colon adenocarcinoma and several lesions in rat liver tissues. An improvement in the histopathological picture was seen in the livers and colons of groups DMHFO17. In conclusion, the present results demonstrated the anti-carciongenic effect of herring fish oil against DMH induced colon carcinogenesis in rats. The inhibitory effect of FO was due to the modulation of elevated biochemical parameters, DNA damage, gene expression and histopathological lesions caused by DMH.

Downloads

Download data is not yet available.

References

Anilakumar KR, Khanum F, Sudarshanakrishna KR, Santhanam K. 2004. Effect of amaranth leaves on dimethylhydrazine-induced changes in multicomponent antioxidant system of rat liver. Indian J. Exp. Biol. 42, 595-600. PMid:15260111

Anti M, Armelao F, Marra G, Percesepe A, Bartoli GM, Palozza P, Parrella P, Canetta C, Gentiloni N, De Vitis I, et al. 1994. Effects of different doses of fish oil on rectal cell proliferation in patients with sporadic colonic adenomas. Gastroenterology 107, 1709-1718. PMid:7958682

Aquardo CF, Noom WA, Begun SJ. 1992. RFLP analysis using heterologous probes. In: Hoelzel, A.R., (ed.), Molecular genetic analysis of populations, a practical approach. IRL press, Oxford., pp. 115-157.

Bancroft JD, Stevens A, Turner DR. 1996. Theory and practice of histological techniques. 4th Ed. New York, Churchill, Livingstone.

Bartoli R, Femandes-Banares F, Navarro E, Castella E, Mane J, Alvarez M, Pastor C, Cabre E, Gassull MA. 2000. Effect of olive oil on early and late events of colon carcinogenesis in rats: modulation of arachidonic acid metabolism and local prostaglandin E2 synthesis. Gut. 46, 191-199 doi:10.1136/gut.46.2.191 PMid:10644312    PMCid:1727832

Boudreau MD, Sohn KH, Rhee SH, Lee SW, Hunt JD Hwang DH. 2001. Suppression of Tumor Cell Growth Both in Nude Mice and in Culture by n-3 Polyunsaturated Fatty Acids: Mediation through Cyclooxygenase-independent Pathways. Cancer Research 61, 1386-1391. PMid:11245439

Brady JF, Li D, Ishizaki H, Yang CS. 1998. Effect of diallyl sulfide on rat liver microsomal nitrosamine metabolism and other monooxygenase activities. Cancer Research 48, 3937-3940.

Buhl SN, Jackson KY. 1978. Optimal conditions and comparison of lactate dehydrogenase catalysis of the lactate-to-pyruvate and pyruvate-to-lactate reactions in human serum at 25, 30, and 37 degrees C. Clin. Chem. 24, 828-31. PMid:25724

Byers T. 1996. Nutrition and cancer among American Indians and Alaska Natives. Cancer 78, 1612-1616. PMid:8839581

Caygil l CP, Hill MJ. 1995. Fish, n-3 fatty acids and human colorectal and breast cancer mortality. Eur. J. Cancer Prev. 4, 329-332. doi:10.1097/00008469-199508000-00008 PMid:7549825

Chang D, Fanwang F, Zhao YS, Pan HZ. 2008. Evaluation of Oxidative Stress in Colorectal Cancer Patients. Biomedical And Environmental Sciences 21, 286-289. doi:10.1016/S0895-3988(08)60043-4

Chang WC, Chapkin RS Lupton JR. 1997. Predictive value of proliferation, differentiation and apoptosis as intermediate markers for colon tumorigenesis. Carcinogenesis 18, 721-730. doi:10.1093/carcin/18.4.721 PMid:9111206

Chang WCL, Chapkin RS, Lupton JR. 1998. Fish oil blocks azoxymethaneinduced rat colon tumorigenesis by increasing cell differentiation and apoptosis rather than decreasing cell proliferation. J. Nutr. 128, 491-497. PMid:9482754

Chapkin RS, Seo J, McMurray DN Lupton JR. 2008. Mechanisms by which docosahexaenoic acid and related fatty acids reduce colon cancer risk and inflammatory disorders of the intestine. Chem. Phys. Lip. 153, 14-23. doi:10.1016/j.chemphyslip.2008.02.011 PMid:18346463    PMCid:2430411

Cheng JL, Futakuchi M, Ogawa K, Iwata T, Kasai M, Tokudome S, Hirose M, Shirai T. 2003. Dose response study of conjugated fatty acid derived from safflower oil on mammary and colon carcinogenesis pretreated with 7,12-dimethylbenz[a]anthracene (DMBA) and 1,2-dimethylhydrazine (DMH) in female Sprague- Dawley rats. Cancer Lett. 196, 161-8. doi:10.1016/S0304-3835(03)00280-5

Choudhary G, Hansen H. 1998. Human health perspective on environmental exposure to hydrazines, a review. Chemosphere, 37, 801-843. doi:10.1016/S0045-6535(98)00088-5

DGKC: Deutsche Gesellschaft fu.r klinische Chemie. Empfehlungen der deutschen Gesellschaft für Klinische Chemie. 1972. Recommendation of the German Society of Clinical Chemistry. Standardization of methods for measurement of enzymatic activities in biological fluids. Z Klin Chem. Klin Biochem. 10, 281-91. PMid:4681028

Dougherty U, Cerasi D, Taylor I, Kocherginsky M, Tekin U, Badal S, Aluri L, Sehdev A, Cerda S, Mustafi R, Delgado J, Joseph L, Zhu H, Hart J, Threadgill D, Fichera A, Bissonnette M. 2009. Epidermal growth factor receptor is required for colonic tumor promotion by dietary fat in the azoxymethane/dextran sulfate sodium model: roles of transforming growth factor-{alpha} and PTGS2. Clin. Cancer Res. 15, 6780-9. doi:10.1158/1078-0432.CCR-09-1678 PMid:19903783    PMCid:2785126

Fisher RA. 1970. Statistical method for research workers, Edinburgh ed. 14, Oliver and Boyed PP. 140-142.

Folch J, Lees M, Sloane-Stanley GH. 1957. A simple method for the isolation and purification of total lipids from animal tissue. J. Biol. Chem. 226, 497 PMid:13428781

Fujise T, Iwakiri R, Kakimoto T, Shiraishi R, Sakata Y, Wu B, Tsunada S, Ootani A, Fujimoto K. 2007. Longterm feeding of various fat diets modulates azoxymethane-induced colon carcinogenesis through Wnt/beta-catenin signaling in rats. Am. J. Physiol. Gastrointest Liver Physiol. 292, G1150-1156. doi:10.1152/ajpgi.00269.2006 PMid:17194898

Gallego FJ, Pérez MA, Núñez Y, Hidalgo P. 2005. Comparison of RAPDs, AFLPs and SSR markers for the genetic analysis of yeast strains of Saccharomyces cerevisiae. Food Microbiol. 22, 561-568. doi:10.1016/j.fm.2004.11.019

Giovannucci E, Willett WC. 1994. Dietary factors and risk of colon cancer. Ann. Med. 26, 443-452. doi:10.3109/07853899409148367 PMid:7695871

Granados S, Quiles JL, Gil A, Ramírez-Tortosa MC. 2006. Dietary lipids and cancer. Nutr. Hosp. 21, 42-54. PMid:16771072

Hill M, Mazal D, Biron VA, Pereira L, Ubillos L, Berriel E, Ahmed H, Freire T, Rondán M, Vasta GR, Liu FT, Iglesias MM, Osinaga E. 2010. A Novel Clinicallyrelevant Animal Model to Study Galectin-3 and Its Ligands During Colon Carcinogenesis. J. Histochem. Cytochem. 58, 553-65. doi:10.1369/jhc.2010.955237 PMid:20197492    PMCid:2874187

Horng YM, Chen YT, Wu CP, Jea YS, Huang MC. 2004. Cloning of Taiwan water buffalo male-specific DNA sequence for sexing. Theriogenology 62, 1536-1543. doi:10.1016/j.theriogenology.2004.02.015 PMid:15451261

Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ. 2003. Cancer Statistics, CA Cancer J. Clin. 53, 5-26. doi:10.3322/canjclin.53.1.5

Jordan A, and Stein J. 2001. Modulation of epidermal growth factor-induced cell proliferation by an omega-3 fatty-acid-containing lipid emulsion on human pancreatic cancer cell line Mia Paca-2. Nutrition 17, 474-475. doi:10.1016/S0899-9007(01)00535-4

Jwanny EW, Moharib SA and Rasmy GE. 2009. Effect of two polysaccharides on chemically-induced colorectal cancer in rats Etidal E. Advances in Food Science 31, 202-209.

Jwanny EW, Salem AM, Moharib SA and Rasmy GE. 2001. Effect of fish oil ethyl esters on hyperlipidemic hamsters. Bull. NRC Egypt. 26, 451-565.

Jwanny EW, Salem AM, Shanab GM and Rasmy GE. 2004. Improved Lipid Lowering Activity of Fibrates On Combination With Fish Oil Ethyl Ester In Hypertriglyceridemic Hamsters. Advances in Food Science 26, 1-10.

Kamaleeswari M, Deeptha K, Sengottuvelan M, and Nalini N. 2006. Effect of dietary caraway (Carum carvi L.) on aberrant crypt foci development, fecal steroids, and intestinal alkaline phosphatase activities in 1,2-dimethylhydrazine-induced colon carcinogenesis. Tox. Appl. Pharmacol. 214, 290-296. doi:10.1016/j.taap.2006.01.001 PMid:16483625

Khalil WKB, Ahmed KA, Park MH, Kim YT, Park HH, Abdel-Wahhab MA. 2008. The inhibitory effects of garlic and Panax ginseng extract standardized with ginsenoside Rg3 on the genotoxicity, biochemical and histological changes induced by Ethylenediaminetetraacetic acid in male rats. Arch. Toxicol. 82,183-195. doi:10.1007/s00204-007-0237-y PMid:17874070

Khalil WKB, Mahmoud MA, Zahran MM, Mahrous KF. 2007. A sub acute study of metronidazole toxicity assessed in Egyptian Tilapia zillii. Journal of Applied Toxicology 27, 380-390. doi:10.1002/jat.1217 PMid:17265432

Kornberg LJ, Villaret D, Popp M, Lui L, McLaren R, Brown H, et al. 2005. Gene expression profiling in squamous cell carcinoma of the oral cavity shows abnormalities in several signaling pathways. Laryngoscope 115, 690-698. doi:10.1097/01.mlg.0000161333.67977.93 PMid:15805883

Latham P, Lund EK and Johnson IT. 1999. Dietary n-3 PUFA increases the apoptotic response to 1,2- dimethylhydrazine, reduces mitosis and suppresses the induction of carcinogenesis in the rat colon. Carcinogenesis 20, 645-650. doi:10.1093/carcin/20.4.645 PMid:10223194

Lee JY and Hwang DH. 2002. Docosahexaenoic acid suppresses the activity of peroxisome proliferatoractivated receptors in a colon tumor cell line. Biochem. Biophys. Res. Comm. 298, 667-674. doi:10.1016/S0006-291X(02)02530-5

Lepage G. and Roy C. 1986. Direct transesterification of all classes of lipids in one-step reaction. J. Lip. Res., 27, 114-120. PMid:3958609

Levin B, Lieberman DA, McFarland B, Smith RA, Brooks D, Andrews KS, Dash C, Giardiello FM, Glick S, Levin TR, Pickhardt P, Rex DK, Thorson A, Winawer SJ. 2008. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J. Clin. 58, 130-60. doi:10.3322/CA.2007.0018 PMid:18322143

Levine AJ. 1997. P53, the cellular gatekeeper for growth and division. Cell 88, 323-331. doi:10.1016/S0092-8674(00)81871-1

Moreira AP, Sabarense CM, Dias CM, Lunz W, Natali AJ, Glória MB, Peluzio MC. 2009. Fish oil ingestion reduces the number of aberrant crypt foci and adenoma in 1,2-dimethylhydrazine-induced colon cancer in rats. Braz. J. Med. Biol. Res. 42, 1167-72. doi:10.1590/S0100-879X2009007500015 PMid:19936544

Nalini N, Manju V, Menon VP. 2004. Effect of coconut cake on the bacterial enzyme activity in 1,2-dimethyl hydrazine induced colon cancer. Clin. Chim. Acta 342, 203-10. doi:10.1016/j.cccn.2004.01.001 PMid:15026282

Narayanan BA, Narayanan NK, Reddy BS. 2001. Docosahexaenoic acid regulated genes and transcription factors inducing apoptosis in human colon cancer cells. Int. J. Oncol. 19, 1255-62. PMid:11713597

Ohkawa H, Ohishi N, Yagi K. 1979. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry 95, 351-358. doi:10.1016/0003-2697(79)90738-3

Parker St, Tong T, Bolden S, Wingo P. 1995. Cancer statistics. CA Cancer J. Clin. 47, 5-27. doi:10.3322/canjclin.47.1.5

Pell JD, Brown JC, Johnson IT. 1994. Polyunsaturated fatty acids of the n-3 series influence intestinal crypt cell production in rats. Carcinogenesis 15, 1115- 1119. doi:10.1093/carcin/15.6.1115 PMid:8020142

Rao CV, Hirose Y, Indranie C, Reddy BS. 2001. Modulation of experimental colon tumorigenesis by types and amounts of dietary fatty acids. Cancer Res. 61, 1927-33. PMid:11280748

Reddy BS, Burill C, Rigotty J. 1991. Effect of diets high in v-3 and v-6 fatty acids on initiation and postinitiation stages of colon carcinogenesis. Cancer Res. 51, 487-491. PMid:1821094

Reddy BS. 2000. Novel approaches to the prevention of colon cancer by nutritional manipulation and chemoprevention. Cancer Epidemiol. Biomarkers Prev. 9, 239-247. PMid:10750661

Reitman S, Frankel S. 1957. A colorimetric method for the determination of serum glutamic oxaloaceytate aminotransferase. Am. J. Clin. Pathol. 28, 56-63. PMid:13458125

Riboli E and Norat T. 2003. Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk. Am. J. Clin. Nutr. 78, 559S-569. PMid:12936950

Rose DP, Connolly JM. 2000. Regulation of tumor angiogenesis by dietary fatty acids and eicosanoids. Nutr. Cancer 37, 119-127. doi:10.1207/S15327914NC372_1 PMid:11142082

Sala-Vila A, Folkes J, Calder PC. 2010. The Effect of Three Lipid Emulsions Differing in Fatty Acid Composition on Growth, Apoptosis and Cell Cycle Arrest in the HT-29 Colorectal Cancer Cell Line. Clin. Nutr., 29, 519-2. doi:10.1016/j.clnu.2009.11.004 PMid:19945772

Sarotra P, Sharma G, Kansal S, Negi AK, Aggarwal R, Sandhir R, Agnihotri N. 2010. Chemopreventive effect of different ratios of fish oil and corn oil in experimental colon carcinogenesis. Lipids 45, 785-98. SAS, 1982. SAS user’s guide: statistics, 1982 edn. SAS Institute Inc., Cary, NC.

Sasaki M, Kato N, Watanabe H, Yamada H. 2000. Silk protein, sericin, suppresses colon carcinogenesis induced by 1,2-dimethylhydrazine in mice. Oncol. Rep. 7, 1049-52. PMid:10948337

Seo T, Blaner WS, Deckelbaum RJ. 2005. N-3 fatty acids: molecular approaches to optimal biological outcomes. Curr. Opin. Lipidol. 16, 11-8. doi:10.1097/00041433-200502000-00004 PMid:15650558

Sharma A, Belna J, Logan J. et al. 2005. The effects of Omega-3 fatty acids on growth regulation of epithelial ovarian cancer cell lines. Gynecol. Oncol. 99, 58. doi:10.1016/j.ygyno.2005.05.024 PMid:16043214

Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D, Warren JT, Bokesch H, Kenney S, Boyd MR. 1990. New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst. 82, 1107-12. doi:10.1093/jnci/82.13.1107

Stoll BA. 2002. N-3 fatty acids and lipid peroxidation in breast cancer inhibition. Br. J. Nutr. 87, 193-8. doi:10.1079/BJN2001512

Tavani A, Pelucchi C, Parpinel M, Negri E, Franceschi S, Levi F, La Vecchia C. 2003. n-3 polyunsaturated fatty acid intake and cancer risk in Italy and Switzerland. Int. J. Cancer 105, 113-116. doi:10.1002/ijc.11018 PMid:12672040

Thapa D, Babu D, Park MA, Kwak MK, Lee YR, Kim JM, Kwon TK, Kim JA. 2010. Induction of p53-independent apoptosis by a novel synthetic hexahydrocannabinol analog is mediated via Sp1-dependent NSAIDactivated gene-1 in colon cancer cells. Biochemical Pharmacology 80, 62-71. doi:10.1016/j.bcp.2010.03.008 PMid:20230799

van Beelen VA, Spenkelink B, Mooibroek H, Sijtsma L, Bosch D, Rietjens IMCM and Alink GM. 2009. An n-3 PUFA-rich microalgal oil diet protects to a similar extent as a fish oil-rich diet against AOM-induced colonic aberrant crypt foci in F344 rats. Food Chem. Tox., 47, 316-320. doi:10.1016/j.fct.2008.11.014 PMid:19049816

Ward JM. 1974. Morphogenesis of chemically induced neoplasm of the colon and small intestine in rats. Lab. Invest. 30, 505-513. PMid:4363166

Watson JL, Hill R, Lee PW, Giacomantonio CA, Hoskin DW. 2008. Curcumin induces apoptosis in HCT-116 human colon cancer cells in a p21-independent manner Exp. Molec. Path. 84, 230-233. doi:10.1016/j.yexmp.2008.02.002 PMid:18423603

WHO report, 2006 on WHO official website: http://www.who.int/research/en/.

Wong R. 2010. Proximal Tumors Are Associated with Greater Mortality in Colon Cancer. J. Gen. Intern. Med. 25, 1157-63. doi:10.1007/s11606-010-1460-4 PMid:20652758

Wu B, Iwakiri R, Ootani A, Tsunada S, Fujise T, Sakata Y, Sakata H, Toda S, Fujimoto K. 2004. Dietary corn oil promotes colon cancer by inhibiting mitochondriadependent apoptosis in azoxymethane-treated rats. Exp. Biol. Med. 229, 1017-1025.

Wynder EL, Kajitani T, Ishikawa S, Dodo H, Takano A. 1969. Environmental factors of cancer of colon and rectum. Cancer 23, 1210-1220. doi:10.1002/1097-0142(196905)23:5<1210::AID-CNCR2820230530>3.0.CO;2-M

Yang P, Felix E, Madden T, Chan D, Newman RA. 2002. Relative formation of PGE2 and PGE3 by eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in human lung cancer cells. Proc. Am. Assoc. Cancer Res. 43: number 1533 (abs.).

Downloads

Published

2011-09-30

How to Cite

1.
Rasmy GE, Khalil WK, Moharib SA, Kawkab AA, Jwanny EW. Dietary fish oil modulates the effect of dimethylhydrazine- induced colon cancer in rats. Grasas aceites [Internet]. 2011Sep.30 [cited 2024Mar.19];62(3):253-67. Available from: https://grasasyaceites.revistas.csic.es/index.php/grasasyaceites/article/view/1323

Issue

Section

Research