A novel animal model to investigate fractionated radiotherapy-induced alimentary mucositis: the role of apoptosis p53 nuclear factor-kappa B COX-1 and COX-2

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dc.contributor.authorYeoh, A.
dc.contributor.authorGibson, R.
dc.contributor.authorYeoh, E.
dc.contributor.authorBowen, J.
dc.contributor.authorStringer, A.
dc.contributor.authorGiam, K.
dc.contributor.authorKeefe, D.
dc.date.issued2007
dc.description© 2007 American Association for Cancer Research
dc.description.abstractRadiation-induced mucositis is a common and serious side effect of radiotherapy. Molecular mechanisms of mucosal injury, however, are still poorly understood and extremely difficult to study in humans. A novel Dark Agouti rat model using fractionated radiotherapy to induce mucositis has been developed to investigate the occurrence of alimentary mucosal injury. Twenty-four Dark Agouti rats were randomly assigned to receive either fractionated radiotherapy or no radiotherapy. The irradiated rats received a fractionated course of abdominal radiotherapy at 45 Gy/18 fractions/6 weeks treating thrice weekly (i.e., at a radiation dose of 2.5 Gy per fraction). After each week of radiation, a group of irradiated rats was killed. Histomorphology and mucin distribution in the alimentary tract was investigated. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay was used to examine apoptosis in the colon and jejunum, and intestinal morphometry was used to assess villus length, crypt length, and mitotic crypt count. Immunohistochemistry of p53, nuclear factor-kappaB, cyclooxygenase (COX)-1, and COX-2 was also done. The fractionated radiotherapy course induced alimentary mucositis from week 1, with more severe injury seen in the small intestine. The hallmark appearance of apoptosis was present in the crypts of the small and large intestine. In the jejunum and colon, goblet cell disorganization and degeneration was obvious and crypt mitotic counts were severely depleted throughout the treatment. Expression of p53, nuclear factor-kappaB, COX-1, and COX-2 was increased in the irradiated intestinal sections. Fractionated radiation-induced alimentary mucositis has been effectively documented in the Dark Agouti rat for the first time. Further studies investigating the molecular mechanisms underlying radiation-induced mucositis are planned to ultimately achieve anti-mucotoxic-targeted therapies.
dc.description.statementofresponsibilityYeoh AS, Gibson RJ, Yeoh EE, Bowen JM, Stringer AM, Giam KA, Keefe DM.
dc.identifier.citationMolecular Cancer Therapeutics, 2007; 6(8):2319-2327
dc.identifier.doi10.1158/1535-7163.MCT-07-0113
dc.identifier.issn1535-7163
dc.identifier.issn1538-8514
dc.identifier.orcidGibson, R. [0000-0002-4796-1621]
dc.identifier.orcidBowen, J. [0000-0003-0876-0031]
dc.identifier.orcidStringer, A. [0000-0003-3245-5360]
dc.identifier.orcidKeefe, D. [0000-0001-9377-431X]
dc.identifier.urihttp://hdl.handle.net/2440/46906
dc.language.isoen
dc.publisherAmer Assoc Cancer Research
dc.source.urihttp://mct.aacrjournals.org/cgi/content/abstract/6/8/2319
dc.subjectDigestive System
dc.subjectColon
dc.subjectIntestine, Small
dc.subjectMicrovilli
dc.subjectAnimals
dc.subjectRats
dc.subjectDisease Models, Animal
dc.subjectNF-kappa B
dc.subjectRadiotherapy
dc.subjectImmunohistochemistry
dc.subjectMitosis
dc.subjectApoptosis
dc.subjectFemale
dc.subjectProstaglandin-Endoperoxide Synthases
dc.subjectTumor Suppressor Protein p53
dc.subjectCyclooxygenase 1
dc.subjectCyclooxygenase 2
dc.subjectMucositis
dc.subjectDose Fractionation, Radiation
dc.titleA novel animal model to investigate fractionated radiotherapy-induced alimentary mucositis: the role of apoptosis p53 nuclear factor-kappa B COX-1 and COX-2
dc.typeJournal article
pubs.publication-statusPublished

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