Development of a New Minipig Model to Study Radiation-Induced Gastrointestinal Syndrome and its Application in Clinical Research
- 1 April 2014
- journal article
- Published by Radiation Research Society in Radiation Research
- Vol. 181 (4), 387-95
- https://doi.org/10.1667/rr13207.1
Abstract
Because of insufficient clinical data regarding acute radiation damage after single high-dose radiation exposure, acute radiation-induced gastrointestinal (GI) syndrome remains difficult to treat. The goal of this study was to establish an appropriate and efficient minipig model to study high-dose radiation-induced GI syndrome after radiation exposure. For endoscopic access to the ileum, ileocutaneous anastomosis was performed 3 weeks before irradiation in six male Göttingen minipigs. Minipigs were locally irradiated at the abdominal area using a gamma source as follows: 1,000 cGy (n = 3) and 1,500 cGy (n = 3). Endoscopic evaluation for the terminal ileum was periodically performed via the ileocutaneous anastomosis tract. Pieces of tissue were serially taken for histological examination. The irradiated intestine presented characteristic morphological changes over time. The most obvious changes in the ileum were mucosal atrophy and telangiectasia from day 1 to day 17 after abdominal irradiation. Microscopic findings were characterized as architectural disorganization, loss of villi and chronic active inflammation. Increase in cyclooxygenase-2 (COX-2) expression was closely correlated with severity of tissue damage and inflammation. Particularly, the plasma citrulline level (PCL), a potential marker for radiation-induced intestinal damage, was significantly decreased the day after irradiation and recovered when irradiated mucosa was normalized. Our results also showed that PCL changes were positively correlated with microscopic changes and the endoscopic score in radiation-induced mucosal damage. In conclusion, the ileocutaneous anastomosis model using the minipig mimics human GI syndrome and allows the study of sequential changes in the ileum, the main target tissue of abdominal irradiation. In addition, PCL could be a simple biomarker for radiation-induced intestinal damage.Keywords
This publication has 23 references indexed in Scilit:
- After the bomb drops: A new look at radiation-induced multiple organ dysfunction syndrome (MODS)International Journal of Radiation Biology, 2011
- The utility of the minipig as an animal model in regulatory toxicologyJournal of Pharmacological and Toxicological Methods, 2010
- Prophylactic feeding with immune-enhanced diet ameliorates chemoradiation-induced gastrointestinal injury in ratsInternational Journal of Radiation Biology, 2010
- Growth factors protect intestinal stem cells from radiation-induced apoptosis by suppressing PUMA through the PI3K/AKT/p53 axisOncogene, 2009
- Pathological changes in the gastrointestinal tract of a heavily radiation-exposed worker at the Tokai-mura criticality accident.Journal of Radiation Research, 2008
- Scope and epidemiology of cancer therapy-induced oral and gastrointestinal mucositisSeminars in Oncology Nursing, 2004
- Abdominal irradiation increases inflammatory cytokine expression and activates NF-κB in rat ileal muscularis layerAmerican Journal of Physiology-Gastrointestinal and Liver Physiology, 2003
- Structural and Functional Alterations of the Gastrointestinal Tract Following Radiation-Induced Injury in the Rhesus MonkeyDigestive Diseases and Sciences, 2002
- Establishment of an Animal Model for Radiation-induced Vomiting in Rats Using PicaJournal of Radiation Research, 2002
- Protocol for the treatment of radiation injuriesAdvances in Space Research, 1992