Abstract
The inhibitory effect of dietary perilla oil rich in the n‐3 polyunsaturated fatty acid α‐linolenic acid against colon carcinogenesis was investigated in rats. Four groups of 26 F344 rats each received an intrarectal dose of 2 mg of N‐methyl‐N‐nitrosourea 3 times a week for 2 weeks, and received a diet containing 12% perilla oil, 6% or 12% safflower oil (rich in the n‐6 polyunsaturated fatty acid linoleic acid), or 12% palm oil (rich in saturated and monounsaturated fatty acids). At week 35, the incidence of colon cancer was significantly lower in perilla oil‐fed rats than in other dietary groups; 19% vs. 46%, 56% and 58%. When examined at week 10, the concentration of fecal bile acids, known to be tumor promoters, was not significantly different among the dietary groups, and the intrarectal deoxycholic acid‐induced colonic mucosal ornithine decarboxylase activity, a marker of tumor promotion, was significantly lower in perilla oil‐fed group than in other groups. The serum and colonic mucosal fatty acid compositions and the blood plasma prostaglandin E2 level directly reflected the fatty acid composition of each dietary fat. The results suggest that the anti‐tumor‐promoting effect of dietary perilla oil was a result of a decreased sensitivity of colonic mucosa to tumor promoters arising from the altered fatty acid composition in membrane phospholipid of colonic epithelial cells, and was not a consequence of a decrease of promoters such as bile acids.
Keywords: Colon carcinogenesis Cancer prevention, Perilla oil, α‐Linolenic acid, Ornithine decarboxylase, Cancer prevention
Full Text
The Full Text of this article is available as a PDF (516.1 KB).
REFERENCES
- 1. ) Weisburger , J. H. and Wynder , E. L.Etiology of colorectal cancer with emphasis on mechanism of action and prevention . In “ Important Advances in Oncology 1987 ,” ed. DeVita V. T., Jr. , Hellman S. and Rosenberg S. A. , pp. 197 – 220 ( 1987. ). J. B. Lippincott Co. , Philadelphia . [PubMed] [Google Scholar]
- 2. ) Wynder , E. L. , Kajitani , T. , Ishikawa , S. , Dodo , H. and Takano , A.Environmental factors of cancer of the colon and rectum . Cancer , 23 , 1210 – 1220 ( 1969. ). [DOI] [PubMed] [Google Scholar]
- 3. ) Reddy , B. S. and Maeura , Y.Tumor promotion by dietary fat in azoxymethane‐induced colon carcinogenesis in female F344 rats: influence of amount and source of dietary fat . J. Natl. Cancer Inst. , 72 , 745 – 750 ( 1984. ). [PubMed] [Google Scholar]
- 4. ) Reddy , B. S. and Maruyama , H.Effect of fish oil on azoxymethane‐induced colon carcinogenesis in male F344 rats . Cancer Res. , 46 , 3367 – 3370 ( 1986. ). [PubMed] [Google Scholar]
- 5. ) Minoura , T. , Takata , T. , Sakaguchi , M , Takada , H. , Yamamura , M. and Yamamoto , M.Effect of dietary eicosapentaenoic acid on azoxymethane‐induced colon carcinogenesis in rats . Cancer Res. , 48 , 4790 – 4794 ( 1988. ). [PubMed] [Google Scholar]
- 6. ) Nelson , R. L. , Tanure , J. C. , Adrianopoulos , G. , Souza , G. and Lands , W. E. M.A comparison of dietary fish oil and corn oil in experimental colorectal carcinogenesis . Nutr. Cancer , 11 , 215 – 220 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Kune , S. , Kune , G. A. and Watson , L. F.Case control study of dietary etiological factors: the Melbourne colorectal cancer study . Nutr. Cancer , 9 , 21 – 42 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 8. ) Tajima , K. , Hirose , K. , Nakagawa , K. , Kuroishi , T. and Tominaga , S.Urban‐rural difference in the trend of colorectal cancer mortality with special reference to the subsites of colon cancer in Japan . Jpn. J. Cancer Res. , 76 , 717 – 728 ( 1985. ). [PubMed] [Google Scholar]
- 9. ) Kinsella , J. E. , Lokesh , B. and Stone , R. A.Dietary n‐3 polyunsaturated fatty acids and amelioration of cardiovascular disease: possible mechanisms . Am. J. Clin. Nutr. , 52 , 1 – 28 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 10. ) Narisawa , T. , Sato , T. , Hayakawa , M. , Sakuma , A. and Nakano , H.Carcinoma of the colon and rectum of rats by rectal infusion of N‐methyl‐N‐nitro‐N‐nitrosoguanidine . Gann , 62 , 231 – 234 ( 1971. ). [PubMed] [Google Scholar]
- 11. ) Stehll , K , D. R. , Lawson , A. M. , Tanida , N. and Sjovall , J.General methods for analysis of metabolic profiles of bile acids and related compounds in feces . J. Lipid Res. , 24 , 1085 – 1100 ( 1983. ). [PubMed] [Google Scholar]
- 12. ) Bligh , E. G. and Dyer , W. J.A rapid method of total lipid extraction and purification . Can. J. Biochem. Physio. , 37 , 911 – 917 ( 1959. ). [DOI] [PubMed] [Google Scholar]
- 13. ) Chida , K. and Kuroki , T.Inhibition of DNA synthesis and sugar uptake and lack of induction of ornithine decarboxylase in human epidermal cells treated with mouse skin tumor promoters . Cancer Res. , 44 , 3226 – 3230 ( 1984. ). [PubMed] [Google Scholar]
- 14. ) Carroll , K. K. and Khor , H. T.Dietary fat in relation to tumorigenesis . Prog. Biochem. Pharmacol. , 10 , 308 – 352 ( 1975. ). [PubMed] [Google Scholar]
- 15. ) Carroll , K. K. and Braden , L. M.Dietary fat and mammary carcinogenesis . Nutr, Cancer , 6 , 245 – 249 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 16. ) Hirose , M. , Masuda , A. , Ito , N. , Kamano , K. and Okuyama , H.Effects of dietary perilla oil, soybean oil and safflower oil on 7, 12‐dimethylbenz(a)anthracene (DMBA) and 1,2‐dimethylhydrazine (DMH)‐induced mammary gland and colon carcinogenesis in female SD rats . Carcinogenesis , 11 , 731 – 735 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 17. ) Awad , A. B. , Chattopadhyay , T. P. and Danahy , M. E.Effect of dietary fat composition on rat colon plasma membrane and fecal lipid . J. Nutr. , 119 , 1376 – 1382 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 18. ) Chautan , M. , Chanussot , F. , Portugal , H. , Pauli , A. M. and Lafont , H.Effects of salmon oil and corn oil on plasma lipid level and hepato‐biliary cholesterol metabolism in rats . Biochim. Biophys. Acta , 1046 , 40 – 45 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 19. ) Reddy , B. S. and Sugie , S.Effect of different levels of omega‐3 and omega‐6 fatty acids on azoxymethane‐induced colon carcinogenesis in F344 rats . Cancer Res. , 48 , 6642 – 6647 ( 1988. ). [PubMed] [Google Scholar]
- 20. ) Stubbs , C. D. and Smith , A. D.The modification of mammalian membrane polyunsaturated fatty acid composition in relation to membrane fluidity and function . Biochim. Biophys. Acta , 779 , 89 – 173 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 21. ) Turini , M. E. , Basu , T. K. and Clandini , M. T.Prostaglandins‐diet‐cancer: a review . Nutr. Res. , 10 , 819 – 827 ( 1990. ). [Google Scholar]
- 22. ) Culp , B. R. , Titus , G. R. and Lands , W. E. M.Inhibition of prostaglandin synthesis by eicosapentaenoic acid . Prostaglandins Med. , 3 , 269 – 278 ( 1979. ). [DOI] [PubMed] [Google Scholar]
- 23. ) Corey , E. J. , Chih , C. and Cashman , J. R.Docosahexaenoic acid is a strong inhibitor of prostaglandin but not leukotriene biosynthesis , Proc. Natl. Acad. Sci. USA , 80 , 3581 – 3584 ( 1983. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. ) Narisawa , T. , Takahashi , M. , Niwa , M. , Fukaura , Y. and Wakizaka , A.Involvement of prostaglandin E2 in bile acid‐caused promotion of colon carcinogenesis and anti‐promotion by the cyclooxygenase inhibitor indomethacin . Jpn. J. Cancer Res. , 78 , 791 – 798 ( 1987. ). [PubMed] [Google Scholar]
- 25. ) Narisawa , T. , Sato , M. , Tani , M. , Kudo , T. , Takahashi , T. and Goto , A.Inhibition of development of methylnitrosourea‐induced rat colon tumors by indomethacin treatment . Cancer Res. , 41 , 1954 – 1957 ( 1981. ). [PubMed] [Google Scholar]
- 26. ) Pollard , M. and Luckert , P. H.Prolonged antitumor effect of indomethacin on autochthonous intestinal tumors in rats . J. Natl. Cancer Inst. , 70 , 1101 – 1105 ( 1983. ). [PubMed] [Google Scholar]
- 27. ) Reddy , B. S. , Maruyama , H. and Kelloff , G.Dose‐related inhibition of colon carcinogenesis by dietary piroxicam, a nonsteroid anti‐inflammatory drug, during different stages of rat colon tumor development . Cancer Res. , 47 , 5340 – 5346 ( 1987. ). [PubMed] [Google Scholar]
- 28. ) Narisawa , T. , Magadia , N. E. , Weisburger , J. H. and Wynder , E. L.Promoting effect of bile acids on colon carcinogenesis after intrarectal instillation of N‐methyl‐N‐nitro‐N‐nitrosoguanidine in rats . J. Natl Cancer Inst. , 53 , 1093 – 1097 ( 1974. ). [DOI] [PubMed] [Google Scholar]
- 29. ) Reddy , B. S. , Watanabe , K. , Weisburger , J. H. and Wynder , E. L.Promoting effect of bile acids in colon carcinogenesis in germ‐free and conventional F344 rats . Cancer Res. , 37 , 3238 – 3242 ( 1977. ). [PubMed] [Google Scholar]
- 30. ) Sarwal , A. N. , Cohen , B. I. , Raicht , R. F. , Takahashi , M. and Fazzini , E.Effect of dietary administration of chenodeoxycholic acid on N‐methyl‐N‐nitrosourea‐induced colon cancer in rats . Biochim. Biophys. Acta , 574 , 423 – 432 ( 1979. ). [DOI] [PubMed] [Google Scholar]
- 31. ) Cohen , B. I. , Raicht , R. F. , Deschner , E. E. , Takahashi , M. , Sarwal , A. N. and Fazzini , E.Effect of cholic acid feeding on N‐methyl‐N‐nitrosourea‐induced colon tumors and cell kinetics in rats . J. Natl. Cancer Inst. , 64 , 573 – 578 ( 1980. ). [PubMed] [Google Scholar]
- 32. ) Deschner , E. E. , Cohen , B. I. and Raicht , R. F.Acute and chronic effect of dietary cholic acid on colonic epithelial cell proliferation . Digestion , 21 , 290 – 296 ( 1981. ). [DOI] [PubMed] [Google Scholar]
- 33. ) Takano , S. , Akagi , M. and Bryan , G. T.Stimulation of ornithine decarboxylase activity and DNA synthesis by phorbol esters or bile acids in rat colon . Gann , 75 , 29 – 35 ( 1984. ). [PubMed] [Google Scholar]
- 34. ) Takano , S. , Matsushima , M. , Ertürk , E. and Bryan , G. T.Early induction of rat colonic epithelial ornithine and S‐adenosyl‐L‐methionine decarboxylase activities by N‐methyl‐N‐nitoro‐N‐nitrosoguanidine and bile salts . Cancer Res. , 41 , 624 – 628 ( 1981. ). [PubMed] [Google Scholar]
- 35. ) Cummings , J. H. , Wiggins , H. S. , Jenkins , D. J. A. , Houston , H. , Jivraj , T. , Drasar , B. S. and Hill , M. J.Influence of diets high or low in animal fat on bowel habit, gastrointestinal transit time, fecal microflora, bile acid and fat excretion . J. Clin. Invest. , 61 , 953 – 963 ( 1978. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36. ) Verma , A. K. , Ashendel , C. L. and Boutwell , R. K.Inhibition by prostaglandin synthesis inhibitors of the induction of epidermal ornithine decarboxylase activity, the accumulation of prostaglandins and tumor promotion caused by 12‐O‐tetradecanoylphorbol‐13‐acetate . Cancer Res. , 40 , 308 – 315 ( 1980. ). [PubMed] [Google Scholar]
- 37. ) Fürstenberger , G. and Marks , F.Indomethacin inhibition of cell proliferation induced by phorbol ester TPA is reversed by prostaglandin E2 in mouse epidermis in vivo . Biochem. Biophys. Res. Commun. , 84 , 1103 – 1111 ( 1978. ). [DOI] [PubMed] [Google Scholar]
- 38. ) Razhin , J. , Wilson , R. S. , Bull , A. W. and Nigro , N. D.Ornithine decarboxylase activity in the rat and human colon . Cancer Res. , 44 , 3226 – 3230 ( 1984. ). [PubMed] [Google Scholar]
- 39. ) Luk , G. D. , Hamilton , S. R. , Yang , P. , Smith , J. A. , O'Ceallaigh , D. , McAvinchey , D. and Hyland , J.Kinetic changes in mucosal ornithine decarboxylase activity during azoxymethane‐induced colon carcinogenesis in rats . Cancer Res. , 46 , 4449 – 4452 ( 1986. ). [PubMed] [Google Scholar]
- 40. ) Sanders , T. A. B.Effects of fish oil on lipid metabolism . Nutrition , 5 , 248 – 250 ( 1989. ). [PubMed] [Google Scholar]
- 41. ) Cho , S. Y. , Miyashita , K. , Miyazawa , T. , Fujimoto , K. and Kanada , T.Autooxidation of ethyl eicosapentaenoate and docosahexaenoate . J. Am. Oil Chem. Soc. , 64 , 876 – 879 ( 1987. ). [Google Scholar]