DMH로 처리한 쥐에서 식이에 첨가한 Conjugated Linoleic Acid 함량에 따라 대장세포의 Apoptosis와 대장암 Biomarker에 미치는 영향

Effect of Different Level of Conjugated Linoleic Acid on Apoptosis of Colonic Mucosal Cell and Biomarkers in Colon Cancer of 1,2-Dimethylhydrazine-Treated Rats

  • 류지혜 (경희대학교 생활과학대학 식품영양학과) ;
  • 윤정한 (한림대학교 생명과학부) ;
  • 하영래 (경상대학교 응용생명과학부) ;
  • 박현서 (경희대학교 생활과학대학 식품영양학과)
  • 발행 : 2002.06.01

초록

The study was designed to compare the anti-carcinogenic effect of different level of conjugated linoleic acid (CLA) in 1,2-dimethylhydrazine (DMH)-treated rats by determining biomarkers (apoptosis, cell proliferation, eicosanoids, 1,2-diacylglycerol) and phospholipid fatty acid profile in colonic mucosa. Eighty male Sprague Dawley rats weighing 180-220g were randomly divided into 4 groups depending on the content of CLA, i.e. 0.0% CLA, 0.5% CLA, 1.0% CLA, 1.5% CLA. The experimental diet contained protein 21.6%, carbohydrate 54.6%, and fat 14.5% including CLA mixture at different level by weight. The experimental diet was fed for 14 weeks with the initiation of intramuscular injection of DMH, which was injected twice a week for 6 weeks to give total amount of 180 mg/kg body weight. Regardless of the amount of CLA supplemented to diet, CLA significantly increased the apoptotic index but did not have significant effect on cell proliferation in colonic mucosa. CLA was undetected in colonic mucosal phospholipid of rats fed the 0% CLA diet and increased to 5.9mg/g phospholipid in rats fed the 0.5% diet. The apoptotic index was increased by 251% and the 1,2-DAG content was decreased by 57% in rats fed 0.5% CLA. No further changes in these variables were observed when CLA in the diet was raised to 1.0% or 1.5%. However, dietary CLA decreased mucosal levels of prostaglandin (PG)E$_2$, thromboxane (TX)B$_2$, and arachidonic acid in dose-dependent manner. The present data indicate that dietary CLA can inhibit DMH-induced colon carcinogenesis by mechanism probably involving increased apoptosis.

키워드

참고문헌

  1. J Agric Food Chem v.37 Newly recognized anticarcinogenic fatty acid: Identification and quantification in natural and processed cheeses Ha,Y.L.;Grimm,N.K.;Pariza,M.W. https://doi.org/10.1021/jf00085a018
  2. Cancer Res v.45 Requirement of essential fatty acid for mammary tumorigenesis in the rat Ip,C.;Carter,C.A.;Ip,M.M.
  3. Carcinogenesis v.17 The efficacy of conjugated linoleic acid in mammary cancer prevention is independent of the level of type of fat in the diet Ip,C.;Briggs,S.;Haegele,A.D.;Thompson,H.J.;Storkson,J.;Scimeca,J.A. https://doi.org/10.1093/carcin/17.5.1045
  4. Cancer Res v.57 Morphological and biochemical status of the mammary gland as influenced by conjugated linoleic acid: implication for a reduction in mammary cancer risk Thompson,H.J.;Zhu,Z.;Banni,S.;Darcy,K.;Loftus,T.;Ip,C.
  5. Lipids v.32 Conjugated linoleic acid modulation of phorbol ester-induced events in murine keratinocyte Liu,K.;Belury,M.A. https://doi.org/10.1007/s11745-997-0092-2
  6. Cancer Res v.50 Inhibition of benzo[a]pyrene-induced mouse forestomach neoplasia by conjugated dienoic derivatives of linoleic acid Ha,Y.L.;Storkson,J.;Pariza,M.W.
  7. Carcinogenesis v.16 Protection of conjugated linoleic acids against 2-amino-3-methyl-limidazo[4,5-f]quinoline-induced colon carcinogenesis in the F344 rat: a study of inhibitory mechanism Liew,H.A.;Shut,H.A.J.;Chin,S.F.;Pariza,M.W.;Dashwood,R.H. https://doi.org/10.1093/carcin/16.12.3037
  8. Mutation Res v.500 Effect of conjugated linoleic acid on the formation of spontaneous and PhIP-induced mutation in the colon and cecum of rats Yang,B.;Glickman,B.W.;Boer,J.G. https://doi.org/10.1016/S0027-5107(02)00002-7
  9. Ph. D. Thesis, Kyung Hee University Effect of dietary supplementation of conjugated linoleic acid on tumor incidence and colon carcinogenesis in 1,2-dimethylhydrazine treated-rats Kim,K.H.
  10. J Cell Biol v.119 Identification of programmed cell death via specific labeling of nuclear DNA fragmentation Gavrieli,Y.;Sherman,Y.;Ben-Sasson,S.A. https://doi.org/10.1083/jcb.119.3.493
  11. J Histochem Cytochem v.35 no.3 Studies with anti-bromodeoxyuridine antibodies: II. Simultaneous immunocytochemical detection of antigen expression and DNA synthesis by in vivo labeling of mouse intestinal mucosa Schutte,B.;Reynders,M.M.;Bosman,F.T.;Blijham,G.H. https://doi.org/10.1177/35.3.3546484
  12. Adv Prostaglandin Thromboxane Res v.5 Quantitative measurement of prostagladins and thromboxanes: general considerations Granstrom,E.;Samuelsson,B.
  13. Methods Biochem Anal v.17 Separation, identification, and estimation of prostaglandins Shaw,J.E.;Ramwell,P.W. https://doi.org/10.1002/9780470110355.ch8
  14. Can J Biochem Physiol v.37 A rapid method of total lipid extraction and purification Bligh,E.G.;Dyer,W.J.
  15. Int J Biochem v.25 An increase in phosophatidic acid in the absence of changes in diacylglycerol in human platelets stimulated with ADP Duncan,E.M.;Lloyd,J.W. https://doi.org/10.1016/0020-711X(93)90485-W
  16. J Lipid Res v.27 Direct trans esterification of all class of lipid in a one step reaction Lepage,G.;Roy,C.C.
  17. Clin Chim Acta v.22 A colorimetric method for estimating serum triglycerides Fletcher,M.J. https://doi.org/10.1016/0009-8981(68)90041-7
  18. Am J Physiol v.273 Physiology and pathophysiology of apoptosis in epithelial cells of the liver, pancreas, and intestine Jones,B.A.;Gores,G.J.
  19. Cancer Epidemiol Biomarkers Prev v.9 Induction of apoptosis by conjugated linoleic acid in cultured mammary tumor cells and premalignant lesions of the rat mammary gland Ip,C.;Ip,M.M.;Loftus,T.;Shoemaker,S.;Shea-Eaton W.
  20. Cancer Epidemiol Biomarkers & Prev v.9 Novel approaches to the prevention of colon cancer by nutritional manipulation and chemoprevention Reddy,B.S.
  21. Biochim Biophys Acta v.1438 Antiplatelet effects of conjugated linoleic acid isomers Truitt,A.;Mcneill,G.;Vanderhoek,J.Y. https://doi.org/10.1016/S1388-1981(99)00055-4
  22. Cancer Letters v.127 Conjugated linoleic acid reduces arachidonic acid content and PGE₂synthesis in murine keratinocytes Liu,K.;Belury,M.A. https://doi.org/10.1016/S0304-3835(97)00479-5
  23. Lipids v.32 Conjugated linoleic acid modulates hepatic lipid composition in mice Belury,M.A.;Kempa-Steczko A. https://doi.org/10.1007/s11745-997-0025-0
  24. Biochim Biophys Acta v.1345 Metabolites of conjugated isomers of linoleic acid (CLA) in the rat Sebedio,J.L.;Juaneda,P.;Dobson,G.;Ramilison,I.;Martin,J.C.;Chardigny,J.M.;Christie,W.W. https://doi.org/10.1016/S0005-2760(97)00015-5
  25. Biochim Biophys Acta v.210 Inhibition of prostaglandin biosynthesis by 8cis, 12trans, 14cis-eicosatrienoic acid and 5cis, 8trans, 12trans, 14cis-eicosatetraenoic acid Nugteren,D.H. https://doi.org/10.1016/0005-2760(70)90072-X
  26. Biochim Biophys Acta v.1580 The effect of conjugated linoelic acid on arachidonic acid metabolism and eicosanoid production in human saphenous vein endothelial cells Urquhart,P.;Parkin,S.M.;Rogers,J.S.;Bosley,J.A.;Nicolaou,A. https://doi.org/10.1016/S1388-1981(01)00198-6
  27. J Natl Cancer Inst v.76 Perspectives on the role of protein kinase C in stimulus-response coupling Nishizuka,Y.
  28. Lipids v.34 Possible mechanism for the putative antiatherogenic and antitumorigenic effects of conjugated polyenoic fatty acid Farquharson,A.;Wu H-C.L.;Grant,I.;Graf,B.;Choung,J.J.;Eremin,O.;Heys,S.;Wahle,K. https://doi.org/10.1007/BF02562337
  29. Biochem Biophys Res Comm v.212 Mechanism of farnesol cytotoxicity: further evidence for the role of PKC-dependent signal transduction in farnesol-induced apoptotic cell death Voziyah,P.A.;Haug,J.S.;Melnykovych,G. https://doi.org/10.1006/bbrc.1995.1995