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

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dc.contributor.authorKerr, C.A.
dc.contributor.authorHines, B.M.
dc.contributor.authorShaw, J.M.
dc.contributor.authorDunne, R.
dc.contributor.authorBragg, L.M.
dc.contributor.authorClarke, J.
dc.contributor.authorLockett, T.
dc.contributor.authorHead, R.
dc.date.issued2013
dc.description.abstractBackground: 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. 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. 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.
dc.identifier.citationBMC Physiology, 2013; 13(2):1-13
dc.identifier.doi10.1186/1472-6793-13-2
dc.identifier.issn1472-6793
dc.identifier.issn1472-6793
dc.identifier.orcidHead, R. [0000-0002-1196-0926]
dc.identifier.urihttps://hdl.handle.net/1959.8/153308
dc.language.isoen
dc.publisherBioMed Central
dc.rightsCopyright 2013 Kerr et al. Licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (http://creativecommons.org/licenses/by/2.0)
dc.source.urihttps://doi.org/10.1186/1472-6793-13-2
dc.subjectazoxymethane
dc.subjectcolorectal cancer
dc.subjectgene expression
dc.subjectrats
dc.subjectIntestinal Mucosa
dc.subjectColon
dc.subjectAnimals
dc.subjectRats, Sprague-Dawley
dc.subjectDNA Damage
dc.subjectGenomics
dc.subjectCell Cycle
dc.subjectApoptosis
dc.subjectTranscription, Genetic
dc.subjectHomeostasis
dc.subjectMale
dc.subjectTumor Suppressor Protein p53
dc.titleGenomic homeostasis is dysregulated in favour of apoptosis in the colonic epithelium of the azoxymethane treated rat
dc.typeJournal article
pubs.publication-statusPublished
ror.fileinfo12143324510001831 13143321650001831 9915909870901831_53108629240001831.pdf
ror.mmsid9915909870901831

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