Abstract A33: Modulation of gene expression by a cooked novel resistant starch in the colon of AOM-treated Fisher 344 rats

Abstract

Abstract We previously reported that a cooked novel steric acid complexed high amylose starch (SAC) diet fed to Azoxymethane (AOM)-treated Fisher 344 rats significantly reduced the preneoplastic lesions, Aberrant Crypt Foci (ACF) and Mucin Depleted Foci (MDF), in comparison with water-boiled normal cornstarch (CS) diet or high amylose cornstarch (HA) diet. To determine the effect of water-boiled SAC diet on the global gene expression patterns we performed Affymetrix Genechip microarray analysis on rat colon mucosa after the rats were treated with AOM and then fed 3 different diets for 8 weeks. Genes that were significantly differentially regulated by AOM or by diet were identified. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was followed as a subsequent examination confirmed the reliability of this analysis. Microarray and qRT-PCR data showed that AOM affected gene expression for 389 genes when considering q<0.1 for AOM effect, i.e., 307 up-regulated and 82 down-regulated genes when comparing AOM-treated water-boiled CS diet group with the same diet group without AOM treatment. Further, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses indicated that most of these differentially expressed genes were associated with several important biological function such as Wnt signaling pathway, TGF-beta signaling pathway, cell cycle, and Chemokine signaling pathways. A genome-wide microarray analysis was also performed to identify the gene expression modulation by water-boiled SAC diet in AOM-treated rats comparing with AOM-treated water-boiled CS diet rats. In this analysis 408 genes were observed as differentially expressed when q<0.01, i.e., 208 up-regulated and 200 down-regulated genes, included in the signaling pathways such as DNA replication, cell cycle, RNA degradation, Steroid biosynthesis, Graft-versus-host disease, Allograft rejection, and Autoimmune thyroid disease pathways. The reliability of the microarray data was further validated by qRT-PCR. These results showed differential regulation of gene expression profiles in Fisher 344 rats fed water-boiled SAC diet compared with normal starch diet. Gene expression modification was also confirmed in the rats treated with AOM. These results provided promising targets for the suppress colonic preneoplastic lesions by SAC starch. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A33.