Chemopreventive n-3 polyunsaturated fatty acids reprogram genetic signatures during colon cancer initiation and progression in the rat

The mechanisms by which n-3 polyunsaturated fatty acids (PUFAs) 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 p...

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Bibliographic Details
Published in:	Cancer research (Chicago, Ill.) Vol. 64; no. 18; pp. 6797 - 6804
Main Authors:	DAVIDSON, Laurie A, NGUYEN, Danh V, CHAPKIN, Robert S, HOKANSON, Regina M, CALLAWAY, Evelyn S, ISETT, Robert B, TURNER, Nancy D, DOUGHERTY, Edward R, NAISYIN WANG, LUPTON, Joanne R, CARROLL, Raymond J
Format:	Journal Article
Language:	English
Published:	Philadelphia, PA American Association for Cancer Research 15-09-2004
Subjects:	Animals Anticarcinogenic Agents - pharmacology Antineoplastic agents Apoptosis - drug effects Azoxymethane Biological and medical sciences Carcinogens Cell Differentiation - drug effects Colonic Neoplasms - genetics Colonic Neoplasms - metabolism Colonic Neoplasms - prevention & control Disease Progression DNA Adducts - antagonists & inhibitors DNA Adducts - biosynthesis Down-Regulation - drug effects Eating - drug effects Fatty Acids, Omega-3 Fatty Acids, Omega-6 - pharmacology Fatty Acids, Unsaturated - pharmacology Fish Oils - pharmacology Gene Expression Profiling Gene Expression Regulation, Neoplastic - drug effects Male Medical sciences Oligonucleotide Array Sequence Analysis Pharmacology. Drug treatments Polymerase Chain Reaction Rats Rats, Sprague-Dawley Triglycerides - pharmacology Tumors Up-Regulation - drug effects Weight Gain - drug effects Rat Rodentia Polyunsaturated fatty acid Lipids Colonic disease Prevention Vertebrata Chemotherapy Mammalia Colon cancer Animal Tumor progression Digestive diseases Intestinal disease Genetics Initiation
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Summary:	The mechanisms by which n-3 polyunsaturated fatty acids (PUFAs) 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 used Codelink DNA microarrays containing approximately 9000 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 hours and 10 weeks after 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 hours and 10-week 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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0008-5472 1538-7445
DOI:	10.1158/0008-5472.can-04-1068