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Butyrate inhibits deoxycholate induced increase in colonic mucosal DNA and protein synthesisIn Vivo

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Diseases of the Colon & Rectum

Abstract

PURPOSE: Crypt surface hyperproliferation is an intermediate biomarker of colon cancer risk.In vitro studies indicate that the short-chain fatty acid and antineoplastic agent butyrate may reverse the crypt surface hyperproliferation induced by the secondary bile acid and tumor promoter, deoxycholate. We hypothesized that butyrate may reverse deoxycholate-induced crypt surface proliferation in vivo.METHODS: Thirty-one Sprague-Dawley rats (250–300 g) underwent surgical isolation of the colon and 24-hour luminal instillation of either sodium chloride, butyrate, deoxycholate, or butyrate plus deoxycholate (all solutions, 2 ml; pH 7; total sodium = 20 mM). Study variables included colon weight, mucosal DNA, mucosal protein, and proliferating cell nuclear antigen immunohistochemistry, labeling of which was determined in five crypt compartments from base to surface (12 crypts per rat). Labeling indexes were calculated as proliferating cell nuclear antigen immunohistochemistry-labeled cells divided by total counted cells in the whole colonic crypt and each of five crypt compartments. The Φ oh value (an index of premalignant risk) was calculated as the ratio of labeled cells in the two surface compartments divided by the total labeled cells. RESULTS: Deoxycholate significantly increased colon wet weight, mucosal protein, total crypt labeling indexes, crypt surface labeling indexes, and the Φ oh value and raised the mucosal DNA content. Butyrate alone slightly reduced total mucosal DNA and protein content. The combination of butyrate plus deoxycholate significantly decreased mucosal DNA and tended to reduce mucosal protein compared with deoxycholate alone. In contrast to prior in vitro findings, butyrate plus deoxycholate did not reverse the deoxycholate-induced surface hyperproliferative changes as measured by proliferating cell nuclear antigen labeling. CONCLUSIONS: Because co-treatment with butyrate plus deoxycholate inhibits deoxycholate-induced increases in total mucosal DNA and protein content, we conclude that butyrate may play a role in maintaining the proliferative balance of the colonic mucosa,in vivo.However, co-treatment with butyrate plus deoxycholate does not reverse the deoxycholate induced increases in colon weight and proliferating cell nuclear antigen labeling indexes under the studied experimental conditions.

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Authors and Affiliations

  1. Harrison Department of Surgical Research, University of Pennsylvania Medical Center, USA

    Omaida C. Velázquez M.D., Renee W. Seto B.A., Julie Choi B.A., Dongying Zhou M.S., Franny Breen B.A., Jason D. Fisher B.A. &  John L. Rombeau M.D.

  2. Department of Surgery, Hospital of the University of Pennsylvania, 4 Silverstein Pavilion, 3400 Spruce Street, 19104, Philadelphia, Pennsylvania

    Omaida C. Velázquez M.D. &  John L. Rombeau M.D.

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  1. Omaida C. Velázquez M.D.
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  2. Renee W. Seto B.A.
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  4. Dongying Zhou M.S.
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  5. Franny Breen B.A.
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  6. Jason D. Fisher B.A.
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  7. John L. Rombeau M.D.
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Additional information

Supported by National Institutes of Health Surgical Oncology Research Training Grant (5T32/CA/096109/08).

Read at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1996, and the Tripartite Meeting, London, United Kingdom, July 3 to 10, 1996.

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Velázquez, O.C., Seto, R.W., Choi, J. et al. Butyrate inhibits deoxycholate induced increase in colonic mucosal DNA and protein synthesisIn Vivo . Dis Colon Rectum 40, 1368–1375 (1997). https://doi.org/10.1007/BF02050825

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  • DOI: https://doi.org/10.1007/BF02050825

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