Abstract
The mechanisms by which n-3 polyunsaturated fatty acids (PUFA) decrease colon tumor
formation have not been fully elucidated. Examination of genes up- or down-regulated at
various stages of tumor development via the monitoring of gene expression relationships will
help to determine the biological processes ultimately responsible for the protective effects of
n-3 PUFA. Therefore, using a 3 x 2 x 2 factorial design, we employed Codelink DNA
microarrays containing ~9,000 genes to help decipher the global changes in colonocyte gene
expression profiles in carcinogen-injected Sprague-Dawley rats. Animals were assigned to
three dietary treatments differing only in the type of fat (corn oil/n-6 PUFA, fish oil/n-3
PUFA or olive oil/n-9 monounsaturated fatty acid), two treatments (injection with the
carcinogen azoxymethane or with saline) and two time points (12 h and 10 wk post first
injection). Only the consumption of n-3 PUFA exerted a protective effect at the initiation
(DNA adduct formation) and promotional (aberrant crypt foci) stages. Importantly,
microarray analysis of colonocyte gene expression profiles discerned fundamental differences
among animals treated with n-3 PUFA at both the 12 h and 10 wk time points. Thus, in
addition to demonstrating that dietary fat composition alters the molecular portrait of gene
expression profiles in the colonic epithelium at both the initiation and promotional stages of
tumor development, these findings indicate that the chemopreventive effect of fish oil is due
to the direct action of n-3 PUFA and not to a reduction in the content of n-6 PUFA.
Full text available at
Cancer Research journal web site.
Data
Data. Complete data set (~18MB).
[Excel Sheet]
Data description. A description of the samples in the above data set is available here.
[PDF]
Tables
Table 1S. Relative colonic gene expression in AOM vs. saline injected rats at the initiation stage.
[PDF]
Table 2S. Relative colonic gene expression in AOM vs. saline injected rats at the promotion stage.
[PDF]
Table 3S. Real Time PCR primers used for confirmation of array results.
[PDF]
Figures
Figure 3S. Expression values of genes with significant differences between
n-3 and n-6 PUFA treatment at 10 wk.
[PDF]
List of 70 genes (probes) in Figure 3S above. [PDF]
Authors
Laurie A. Davidson3,4,
Danh V. Nguyen5,
Regina M.Hokanson4,
Evelyn S. Callaway3,
Robert B. Isett4,
Nancy D. Turner3,4,
Edward R. Dougherty6,
Naisyin Wang7,
Joanne R. Lupton3,4,
Raymond J. Carroll4,7,
Robert S. Chapkin3,4
3Faculty of Nutrition, Texas A&M University, College Station, TX 77843-2471
4Center for Environmental and Rural Health, Texas A&M University, College Station, TX 77843-4455
5Division of Biostatistics, University of California School of Medicine, Davis, CA 95616-8638
6Department of Electrical Engineering, Texas A&M University 77843-3128
7Department of Statistics, Texas A&M University, College Station, TX 77843-3143
1This work was supported in part by NIH grants CA59034, CA57030, CA61750, NIEHS P30-
ES09106 and Life Sciences Enhancement Funds, Texas A&M University.
2Address correspondence to: Dr. Robert S. Chapkin
Molecular and Cell Biology Section, Faculty of Nutrition
442 Kleberg Center
TAMU 2471
Texas A&M University
College Station, TX 77843-2471
Phone: 979-845-0419
Fax: 979-862-2662
e-mail: r-chapkin@tamu.edu
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