This Article 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 Boffa, L. C. Articles by Lipkin, M. Search for Related Content PubMed PubMed Citation Articles by Boffa, L. C. Articles by Lipkin, M.

Modulation of Colonic Epithelial Cell Proliferation, Histone Acetylation, and Luminal Short Chain Fatty Acids by Variation of Dietary Fiber (Wheat Bran) in Rats¹

Department of Chemical Carcinogenesis, Istituto Nazionale per la Ricerca sul Cancro, IST, 16132 Genoa, Italy [L. C. B., M. R. M., M. C.]; Irving Weinstein Laboratory for Gastrointestinal Cancer Prevention, Gastroenterology and Nutrition Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 [A. S., H. L. N., M. L.]; and Faculty of Nutrition, Texas A&M University, College Station, Texas 77843-2471 [J. R. L.]

The effect of increasing amounts of wheat bran (0, 5, 10, 20%) in AIN-76 semisynthetic diet on colonic luminal short chain fatty acids, epithelial cell histone acetylation, and cytokinetics, was studied for 2 weeks in groups of 10 male Sprague-Dawley rats. Luminal contents were removed from the colon at sacrifice, quick frozen, and analyzed for short chain fatty acids by gas-liquid chromatography. Histone acetylation was assessed in cells isolated from the same animals. Cell proliferation was measured after a short pulse in vivo with [³H]thymidine. Colonic luminal butyrate levels were lower in the 0 and 20% fiber groups, and higher in the 5 and 10% fiber groups. In contrast, cell proliferation, as determined by labeling index, was higher in the 0 and 20% fiber groups, and lower in the 5 and 10% fiber groups. This resulted in a significant inverse correlation between luminal butyrate levels and colonic cell proliferation. In addition, there was a positive linear correlation between luminal butyric acid levels and colon epithelial cell histone acetylation. From these data it was concluded that colonic butyrate levels can be modulated by the addition of wheat bran to the diet and that butyrate can modulate DNA synthesis (calculated as labeling index) in the proliferative compartments of colonic crypts. The localization of dividing cells was unchanged and no induction of terminal differentiation was detectable (contrary to what has been observed for transformed cells in culture).

¹ Supported in part by Associazione Italiana per la Ricerca sul Cancro (AIRC 1990–92) (L. C. B.), American Cancer Society Grant SIG-7A (M. L.), and American Institute for Cancer Research (J. R. L.).

² To whom requests for reprints should be addressed, at Department of Chemical Carcinogenesis, Istituto Nazionale per la Ricerca sul Cancro, IST, Viale Benedetto XV no. 10, 16132 Genoa, Italy.

Received 8/10/92. Accepted 8/24/92.

This article has been cited by other articles:

				C. L. Kien, C. P. Peltier, S. Mandal, J. R. Davie, and R. Blauwiekel Effects of the In Vivo Supply of Butyrate on Histone Acetylation of Cecum in Piglets JPEN J Parenter Enteral Nutr, January 1, 2008; 32(1): 51 - 56. [Abstract] [Full Text] [PDF]

				B. L. Pool-Zobel, V. Selvaraju, J. Sauer, T. Kautenburger, J. Kiefer, K. K. Richter, M. Soom, and S. Wolfl Butyrate may enhance toxicological defence in primary, adenoma and tumor human colon cells by favourably modulating expression of glutathione S-transferases genes, an approach in nutrigenomics Carcinogenesis, June 1, 2005; 26(6): 1064 - 1076. [Abstract] [Full Text] [PDF]

				N. M. Moreau, M. M. Champ, S. M. Goupry, B. J. Le Bizec, M. Krempf, P. G. Nguyen, H. J. Dumon, and L. J. Martin Resistant Starch Modulates In Vivo Colonic Butyrate Uptake and Its Oxidation in Rats with Dextran Sulfate Sodium-Induced Colitis J. Nutr., March 1, 2004; 134(3): 493 - 500. [Abstract] [Full Text] [PDF]

				T.J. Collard, M. Guy, A.J. Butt, C.M. Perks, J.M.P. Holly, C. Paraskeva, and A.C. Williams Transcriptional upregulation of the insulin-like growth factor binding protein IGFBP-3 by sodium butyrate increases IGF-independent apoptosis in human colonic adenoma-derived epithelial cells Carcinogenesis, March 1, 2003; 24(3): 393 - 401. [Abstract] [Full Text] [PDF]

				B. F. Hinnebusch, S. Meng, J. T. Wu, S. Y. Archer, and R. A. Hodin The Effects of Short-Chain Fatty Acids on Human Colon Cancer Cell Phenotype Are Associated with Histone Hyperacetylation J. Nutr., May 1, 2002; 132(5): 1012 - 1017. [Abstract] [Full Text] [PDF]

				M. W. Musch, C. Bookstein, Y. Xie, J. H. Sellin, and E. B. Chang SCFA increase intestinal Na absorption by induction of NHE3 in rat colon and human intestinal C2/bbe cells Am J Physiol Gastrointest Liver Physiol, April 1, 2001; 280(4): G687 - G693. [Abstract] [Full Text] [PDF]

				J. T. Wu, S. Y. Archer, B. Hinnebusch, S. Meng, and R. A. Hodin Transient vs. prolonged histone hyperacetylation: effects on colon cancer cell growth, differentiation, and apoptosis Am J Physiol Gastrointest Liver Physiol, March 1, 2001; 280(3): G482 - G490. [Abstract] [Full Text] [PDF]

				C. Hadjiagapiou, L. Schmidt, P. K. Dudeja, T. J. Layden, and K. Ramaswamy Mechanism(s) of butyrate transport in Caco-2 cells: role of monocarboxylate transporter 1 Am J Physiol Gastrointest Liver Physiol, October 1, 2000; 279(4): G775 - G780. [Abstract] [Full Text] [PDF]

				J. M. Mariadason, G. A. Corner, and L. H. Augenlicht Genetic Reprogramming in Pathways of Colonic Cell Maturation Induced by Short Chain Fatty Acids: Comparison with Trichostatin A, Sulindac, and Curcumin and Implications for Chemoprevention of Colon Cancer Cancer Res., August 1, 2000; 60(16): 4561 - 4572. [Abstract] [Full Text]

				B. A. Magnuson, M. Davis, S. Hubele, P. R. Austin, I. T. Kudva, C. J. Williams, C. W. Hunt, and C. J. Hovde Ruminant Gastrointestinal Cell Proliferation and Clearance of Escherichia coli O157:H7 Infect. Immun., July 1, 2000; 68(7): 3808 - 3814. [Abstract] [Full Text] [PDF]

				F. Chai, A. Evdokiou, G.P. Young, and P.D. Zalewski Involvement of p21Waf1/Cip1 and its cleavage by DEVD-caspase during apoptosis of colorectal cancer cells induced by butyrate Carcinogenesis, January 1, 2000; 21(1): 7 - 14. [Abstract] [Full Text] [PDF]

				L. E. Harrison, Q. M. Wang, and G. P. Studzinski Butyrate-Induced G2/M Block in Caco-2 Colon Cancer Cells is Associated with Decreased p34cdc2 Activity Experimental Biology and Medicine, November 1, 1999; 222(2): 150 - 156. [Abstract] [Full Text]

				H. Huang, C. P. Reed, J.-S. Zhang, V. Shridhar, L. Wang, and D. I. Smith Carboxypeptidase A3 (CPA3): A Novel Gene Highly Induced by Histone Deacetylase Inhibitors during Differentiation of Prostate Epithelial Cancer Cells Cancer Res., June 1, 1999; 59(12): 2981 - 2988. [Abstract] [Full Text] [PDF]

				G. Caderni, D. Palli, L. Lancioni, A. Russo, C. Luceri, C. Saieva, G. Trallori, L. Manneschi, F. Renai, S. Zacchi, et al. Dietary Determinants of Colorectal Proliferation in the Normal Mucosa of Subjects with Previous Colon Adenomas Cancer Epidemiol. Biomarkers Prev., March 1, 1999; 8(3): 219 - 225. [Abstract] [Full Text] [PDF]

				S. Y. Archer, S. Meng, A. Shei, and R. A. Hodin p21WAF1 is required for butyrate-mediated growth inhibition of human colon cancer cells PNAS, June 9, 1998; 95(12): 6791 - 6796. [Abstract] [Full Text] [PDF]

				H. Ichikawa and T. Sakata Stimulation of Epithelial Cell Proliferation of Isolated Distal Colon of Rats by Continuous Colonic Infusion of Ammonia or Short-Chain Fatty Acids Is Nonadditive J. Nutr., May 1, 1998; 128(5): 843 - 847. [Abstract] [Full Text]

				L. Yin, G. Laevsky, and C. Giardina Butyrate Suppression of Colonocyte NF-kappa B Activation and Cellular Proteasome Activity J. Biol. Chem., November 21, 2001; 276(48): 44641 - 44646. [Abstract] [Full Text] [PDF]