RGD Reference Report - A novel animal model to investigate fractionated radiotherapy-induced alimentary mucositis: the role of apoptosis, p53, nuclear factor-kappaB, COX-1, and COX-2. - Rat Genome Database

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

Authors: Yeoh, AS  Gibson, RJ  Yeoh, EE  Bowen, JM  Stringer, AM  Giam, KA  Keefe, DM 
Citation: Yeoh AS, etal., Mol Cancer Ther. 2007 Aug;6(8):2319-27.
RGD ID: 2290567
Pubmed: PMID:17699727   (View Abstract at PubMed)
DOI: DOI:10.1158/1535-7163.MCT-07-0113   (Journal Full-text)

Radiation-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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTGS1HumanExperimental Radiation Injuries  ISOPtgs1 (Rattus norvegicus)protein:increased expression:intestineRGD 
PTGS2HumanExperimental Radiation Injuries  ISOPtgs2 (Rattus norvegicus)protein:increased expression:intestineRGD 
Ptgs1RatExperimental Radiation Injuries  IEP protein:increased expression:intestineRGD 
Ptgs1MouseExperimental Radiation Injuries  ISOPtgs1 (Rattus norvegicus)protein:increased expression:intestineRGD 
Ptgs2RatExperimental Radiation Injuries  IEP protein:increased expression:intestineRGD 
Ptgs2MouseExperimental Radiation Injuries  ISOPtgs2 (Rattus norvegicus)protein:increased expression:intestineRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Tp53Ratresponse to X-ray  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptgs1  (prostaglandin-endoperoxide synthase 1)
Ptgs2  (prostaglandin-endoperoxide synthase 2)
Tp53  (tumor protein p53)

Genes (Mus musculus)
Ptgs1  (prostaglandin-endoperoxide synthase 1)
Ptgs2  (prostaglandin-endoperoxide synthase 2)

Genes (Homo sapiens)
PTGS1  (prostaglandin-endoperoxide synthase 1)
PTGS2  (prostaglandin-endoperoxide synthase 2)


Additional Information