Duodenogastric reflux and foregut carcinogenesis: analysis of duodenal juice in a rodent model of cancer

The incidence of esophageal adenocarcinoma is increasing rapidly. In rats, surgically induced duodenoesophageal reflux is carcinogenic. One proposed m echanism of carcinogenesis is based on the reaction of physiological bile a cids with nitrite to produce carcinogenic N-nitroso amides, To test this hy pothesis, duodenal juice was analyzed for endogenously formed N-nitroso bil e acids and its genotoxicity was determined. Esophagojejunostomy was perfor med on 15 Sprague-Dawley rats to produce duodenoesophageal reflux. At the t ime of surgery and 2 and 6 weeks later, duodenal contents were aspirated an d analyzed immediately. Nigh performance liquid chromatography coupled to t andem mass spectrometry was used to detect bile acids and their nitroso der ivates, Genotoxicity was assessed using a micronucleus test, The characteri stic pattern of bile acid derivatives, with taurocholic acid (TCA) and glyc ocholic acid (GCA) as the predominant conjugates, was detected in all sampl es. However, even selective reaction monitoring experiments failed to demon strate the presence of any N-nitroso-TCA or N-nitroso-GCA. In addition, oth er nitroso derivatives could not be detected in any of the samples by neutr al loss experiments monitoring the loss of nitric oxide (detection limit 0. 1% of the concentration of TCA). All samples were cytotoxic, but neither th e preoperative nor the postoperative samples were genotoxic. Duodenal juice was cytotoxic but not genotoxic, Tumorigenesis of esophageal adenocarcinom a in the rodent model could not be linked to a specific carcinogen, especia lly not to nitroso bile acids. Chronic inflammation is likely to be the mec hanism of carcinogenesis by duodenogastric reflux.