The broad scientific goal of this interactive research program is to evolve a systematic biochemical understanding of how the consumption of fibers, fats, and proteins results in colonic epithelial cells that are more or less susceptible to chemical carcinogens. The focus of this proposal is on short chain fatty acids (SCFA) which are the products of fiber fermentation. Using cells from both carcinogen-treated and saline control animals, we propose to characterize how uptake of SCFA into colonocytes changes the biochemistry of these cells in such a way that their proliferative status is altered. The three important changes in biological/biochemical states that will be investigated are: (1) changes in intracellular pH; (2) changes in colonocyte metabolism (including energy status); and (3) changes in membrane lipids that result in changes in signal transduction pathways (specifically Protein Kinase C, isoforms and subcellular localization). Since there is good evidence that the effect of SCFA on colonocytes is different in normal cells vs transformed cells, experiments will be conducted in both cell types. Further, since the proximal and distal colon have different cell kinetics and SCFA absorption patterns, they will be treated as separate tissues. The data generated will elucidate how intracellular pH, colonocyte metabolism, and intracellular signaling mechanisms, which regulate epithelial cytokinetics, are influenced by different types and amounts of SCFA characterization of each part of this complex process should provide important information on the basic biology of colonocytes. Elucidation of the fundamental mechanisms regulating colonic epithelial cytokinetics is essential if diet is to be established as a legitimate colon cancer prevention strategy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA061750-01
Application #
2102514
Study Section
Special Emphasis Panel (SRC (70))
Project Start
1994-08-01
Project End
1999-05-31
Budget Start
1994-08-01
Budget End
1995-05-31
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Texas Agrilife Research
Department
Veterinary Sciences
Type
Schools of Earth Sciences/Natur
DUNS #
110521739
City
College Station
State
TX
Country
United States
Zip Code
77843
Hong, Mee Young; Turner, Nancy D; Murphy, Mary E et al. (2015) In vivo regulation of colonic cell proliferation, differentiation, apoptosis, and P27Kip1 by dietary fish oil and butyrate in rats. Cancer Prev Res (Phila) 8:1076-83
Cho, Youngmi; Turner, Nancy D; Davidson, Laurie A et al. (2014) Colon cancer cell apoptosis is induced by combined exposure to the n-3 fatty acid docosahexaenoic acid and butyrate through promoter methylation. Exp Biol Med (Maywood) 239:302-10
Cho, Youngmi; Turner, Nancy D; Davidson, Laurie A et al. (2012) A chemoprotective fish oil/pectin diet enhances apoptosis via Bcl-2 promoter methylation in rat azoxymethane-induced carcinomas. Exp Biol Med (Maywood) 237:1387-93
Cho, Youngmi; Kim, Hyemee; Turner, Nancy D et al. (2011) A chemoprotective fish oil- and pectin-containing diet temporally alters gene expression profiles in exfoliated rat colonocytes throughout oncogenesis. J Nutr 141:1029-35
Vanamala, J; Glagolenko, A; Yang, P et al. (2008) Dietary fish oil and pectin enhance colonocyte apoptosis in part through suppression of PPARdelta/PGE2 and elevation of PGE3. Carcinogenesis 29:790-6
Apanasovich, Tatiyana V; Ruppert, David; Lupton, Joanne R et al. (2008) Aberrant crypt foci and semiparametric modeling of correlated binary data. Biometrics 64:490-500
Crim, Kristy Covert; Sanders, Lisa M; Hong, Mee Young et al. (2008) Upregulation of p21Waf1/Cip1 expression in vivo by butyrate administration can be chemoprotective or chemopromotive depending on the lipid component of the diet. Carcinogenesis 29:1415-20
Baladandayuthapani, Veerabhadran; Mallick, Bani K; Young Hong, Mee et al. (2008) Bayesian hierarchical spatially correlated functional data analysis with application to colon carcinogenesis. Biometrics 64:64-73
Hong, Mee Young; Turner, Nancy D; Carroll, Raymond J et al. (2005) Differential response to DNA damage may explain different cancer susceptibility between small and large intestine. Exp Biol Med (Maywood) 230:464-71
Hong, Mee Young; Bancroft, Laura K; Turner, Nancy D et al. (2005) Fish oil decreases oxidative DNA damage by enhancing apoptosis in rat colon. Nutr Cancer 52:166-75

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