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

Authors
  • Kerr, Caroline A1, 2, 3
  • Hines, Barney M1, 4
  • Shaw, Janet M1, 2
  • Dunne, Robert1, 5
  • Bragg, Lauren M1, 5
  • Clarke, Julie1, 6
  • Lockett, Trevor1, 2
  • Head, Richard1
  • 1 CSIRO Preventative Health Flagship, CSIRO, North Ryde, NSW, 2113, Australia , North Ryde (Australia)
  • 2 CSIRO, Food and Nutritional Sciences, North Ryde, NSW, 2113, Australia , North Ryde (Australia)
  • 3 University of Wollongong, Graduate School of Medicine, Wollongong, NSW, Australia , Wollongong (Australia)
  • 4 CSIRO Division of Livestock Industries, Queensland Biosciences Precinct, St Lucia, Queensland, 4067, Australia , St Lucia (Australia)
  • 5 CSIRO, Mathematical and Information Sciences, North Ryde, New South Wales, 1670, Australia , North Ryde (Australia)
  • 6 CSIRO Food and Nutritional Sciences, Adelaide, 5000, South Australia , Adelaide (Australia)
Type
Published Article
Journal
BMC Physiology
Publisher
BioMed Central
Publication Date
Jan 23, 2013
Volume
13
Issue
1
Identifiers
DOI: 10.1186/1472-6793-13-2
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundThe 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.ResultsThere 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.ConclusionsThe 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.

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