Ingestion of thioproline suppresses rat esophageal adenocarcinogenesis caused by duodenogastroesophageal reflux

Duodenogastroesophageal reflux causes esophageal adenocarcinoma in rats without the use of a carcinogen. This etiology is unclear, but may be associated with endogenous nitrosation in the gastrointestinal tract. Thioproline (TPRO) is an effective nitrite-trapping agent and blocks endogenous nitrosation. We investigated how ingested TPRO affected esophageal adenocarcinogenesis in rats with duodenogastroesophageal reflux (DGER) or gastroesophageal reflux (GER). A series of 200 male Fischer 344 rats received surgery to induce reflux of duodenogastric contents or gastric contents alone into the esophagus. The rats were separated into two divisions according to the surgical procedure employed (DGER or GER), and each division was further subdivided into two groups: one group was fed a special diet (CRF-1 containing 0.5% of TPRO); the other group was fed a standard diet (CRF-1). The rats were given no carcinogen and sacrificed at ten-week intervals from the 25th to the 45th week after surgery. Pathological examination was carried out using hematoxylin-eosin or immunohistochemical staining. Erosion, regenerative thickening, basal cell hyperplasia and columnar-lined epithelium (CLE) were found in both groups of the DGER rats. Adenocarcinoma (AC) appeared only in the DGER rats sacrificed at 35 and 45 weeks following surgery. The incidence of AC at the 45th week was significantly lower in the group of rats fed the diet containing TPRO, as compared to those fed the standard diet, whereas the incidences of CLE were the same for both groups. iNOS protein and nitrotyrosine protein were identified in the CLE and macrophages of the DGER group using immunohistochemical staining. There were no remarkable pathological changes in the esophagi of the rats which underwent the GER procedure. In conclustion, TPRO has an inhibitory effect on esophageal reflux-induced adenocarcinogenesis in rats in that it prevents the progression from CLE to AC.