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Open Access Research article

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

Caroline A Kerr126*, Barney M Hines13, Janet M Shaw12, Robert Dunne14, Lauren M Bragg14, Julie Clarke15, Trevor Lockett12 and Richard Head1

Author Affiliations

1 CSIRO Preventative Health Flagship, CSIRO, North Ryde, NSW 2113, Australia

2 CSIRO, Food and Nutritional Sciences, North Ryde, NSW 2113, Australia

3 CSIRO Division of Livestock Industries, Queensland Biosciences Precinct, St Lucia, Queensland 4067, Australia

4 CSIRO, Mathematical and Information Sciences, North Ryde, New South Wales 1670, Australia

5 CSIRO Food and Nutritional Sciences, Adelaide 5000, South Australia

6 Graduate School of Medicine, University of Wollongong, Wollongong, NSW, Australia

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BMC Physiology 2013, 13:2  doi:10.1186/1472-6793-13-2

Published: 23 January 2013

Abstract

Background

The acute response to genotoxic carcinogens in rats is an important model for researching cancer initiation events. In this report we define the normal rat colonic epithelium by describing transcriptional events along the anterior-posterior axis and then investigate the acute effects of azoxymethane (AOM) on gene expression, with a particular emphasis on pathways associated with the maintenance of genomic integrity in the proximal and distal compartments using whole genome expression microarrays.

Results

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.

Conclusions

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.

Keywords:
Colorectal cancer; Azoxymethane; Rats; Gene expression