Genomic homeostasis is dysregulated in favour of apoptosis in the colonic epithelium of the azoxymethane treated rat

There are large transcriptional changes that occur in epithelial gene expression along the anterior-posterior axis of the normal healthy rat colon. AOM administration superimposes substantial changes on these basal gene expression patterns in both the distal and proximal rat colonic epithelium. In particular, the pathways associated with cell cycle and DNA damage and repair processes appear to be disrupted in favour of apoptosis.The healthy rats’ colon exhibits extensive gene expression changes between its proximal and distal ends. The most common changes are associated with metabolism, but more subtle expression changes in genes involved in genomic homeostasis are also evident. These latter changes presumably protect and maintain a healthy colonic epithelium against incidental dietary and environmental insults. AOM induces substantial changes in gene expression, resulting in an early switch in the cell cycle process, involving p53 signalling, towards cell cycle arrest leading to the more effective process of apoptosis to counteract this genotoxic insult.Colorectal cancer (CRC) is the third most common cancer in males and second most common in females world-wide [1]. The majority of these cancers are considered preventable by appropriate diet and associated lifestyle factors [2]. Dietary patterns consisting of micronutrient dense, low-fat, high-fibre food patterns protect against colorectal cancer [3,4]. Conversely, specific sources of dietary protein have been linked to increased CRC risk [5] and animal studies have indicated that different dietary proteins can induce DNA damage in the rats’ colon [6]. Consequently, the challenge is to translate this information into strategies that prevent CRC. One of the first steps to doing this is to understand the early molecular events involved in oncogenesis and develop hypotheses on the role played by environmental factors such as diet in this process.The azoxymethane (AOM)-treated rodent provides an important tool in the s