Background and aim: It is known that bile acids can induce mucosal injury, stimulate cell proliferation, and promote tumorigenesis. A large body of genetic and biochemical evidence indicate that the biosynthetic pathway of prostaglandin E 2 (PGE 2 ) may play an important role in human and rodent tumours. Therefore, we examined the expression pattern of cyclooxygenase 1 (COX-1), COX-2, and microsomal prostaglandin E synthase 1 (mPGES-1), as well as EP receptor subtypes in rat oesophageal lesions induced by duodenal contents reflux. Methods: Oesophagoduodenal anastomosis was performed in rats to induce duodenal contents reflux. We examined histological changes and expression of COX-1, COX-2, mPGES-1, and EP receptor subtypes in the oesophagus by immunohistochemistry and reverse transcription-polymerase chain reaction. Results: Normal control oesophageal tissues showed COX-1 expression in subepithelial stromal cells, including endothelial cells and muscular cells, and did not reveal expression of COX-2 or mPGES-1. In the case of squamous cell lesions, immunoreactivity of COX-1 was similar to that of normal lesions, and COX-2 was maximally expressed around the vascular papillae of tissues showing dysplasia and surrounding epithelial layer and basal layer. mPGES-1 was highly expressed in stromal cells with COX-2 expression. In the case of Barrett's oesophagus, COX-2 and mPGES-1 were predominantly in subepithelial stromal cells. mRNA levels of COX-2, mPGES-1, EP 2 , EP 3 , and EP 4 were higher in the experimental groups than in controls. Conclusions: We suggest that the biosynthetic pathway of PGE 2 may play an important role in oesophageal squamous cell dysplasia and glandular metaplasia induced by duodenal contents reflux.

Barrett's esophagus is a premalignant condition of esophageal adenocarcinoma. Inducible nitric oxide synthase (iNOS) is induced by cytokines and can generate locally high concentrations of nitric oxide (NO), whose metabolites can mediate genotoxicity and influence multistage carcinogenesis by causing DNA damage. Therefore, we evaluated the immunolocalization and expression of iNOS in surgically induced rat Barrett's esophagus. Esophagoduodenal anastomosis was performed in rats for inducing reflux of duodenal contents. Rats were killed at postoperative 10, 20, 30 and 40 weeks. We examined histologic changes and iNOS expression in esophagus by immunohistochemistry and reverse transcription-polymerase chain reaction. Eighty six percent of experimental rats showed Barrett's esophagus above esophagoduodenal junction. iNOS immunoreactivity was clearly observed in the epithelial cells of Barrett's esophagus, predominantly at the apical surface of epithelial cells. Cytoplasmic staining was also seen only in atypical Barrett's esophagus. iNOS mRNA was detected only in the lower esophagus of experimental group. In conclusion, this study suggests that iNOS has some roles on Barrett's esophagus formation.