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Dietary wheat bran protects against induced colon carcinogenesis: an examination of potential mechanisms
Dissertation   Open access

Dietary wheat bran protects against induced colon carcinogenesis: an examination of potential mechanisms

Dana Charlene Widener Compher
Doctor of Philosophy (Ph.D.), Drexel University
Jun 1999
DOI:
https://doi.org/10.17918/00000632
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Abstract

We hypothesized that the protective effects of wheat bran against colon cancer may be due to increased production of colonic butyrate, and that the presence of colonic butyrate will decrease crypt surface proliferation, increase apoptosis, and decrease cyclooxygenase 2 expression. Butyrate, a short-chain fatty acid produced by bacterial anaerobic fermentation of wheat bran's non-starch polysaccharde components, is an anti-neoplastic mediator with colon cancer cells in vitro. The F344 rat, induced with the chemical carcinogen azoxymethane, was used to examine the effects of 20% wheat bran added to a typical high fat western diet on measures of proliferation and cell death at tumor initiation as well as on aberrant crypt foci at tumor promotion. Fecal butyrate concentrations were measured by gas chromatography/mass spectrometry. Levels of apoptosis, proliferation and cyclooxygenase 2 expression were detected in colonic epithelial cells by immunohistochemistry. Wheat bran increased apoptosis and controlled crypt surface hyperproliferation at tumor initiation. Wheat bran limited apical proliferation at tumor promotion, maintaining the normal zone of proliferation. No differences in COX2 protein were detected for the diet treatment. COX2 levels were increased at tumor initiation, but COX2 in proximal colon had resolved by tumor promotion. COX1 was reduced by wheat bran at tumor initiation, particularly in proximal colon. Total cyclooxygenase protein at tumor initiation was thus reduced, and may have limited carcinogen activation. Aberrant crypt foci were significantly reduced by the wheat bran diet. Both diet groups had fewer aberrant crypts in proximal than distal colon, consistent with the butyrate gradient down the colon. Fecal butyrate levels were increased by the wheat bran diet throughout the experiments, suggesting a role of butyrate as anti-neoplastic mediator of wheat bran ingestion. The important application of these research findings is toward a mechanistic understanding of chemopreventive properties of wheat bran against human colorectal cancer. These data suggest that, even with a typical high fat western diet, colon cancer development can be modulated by ingestion of wheat bran.

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