2000 Abstract: 2251: Duodenogastric Reflux and Foregut Carcinogenesis: Analysis of the Duodenal Juice in the Rodent Cancer Model.
Abstracts
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Purpose: The incidence of esophageal adenocarcinoma is rapidly increasing. In the rodent cancer model surgically induced duodenoesophageal reflux is carcinogenic. One proposed mechanism of carcinogenesis relies on the reaction of physiologic bile acids with nitrite to produce carcinogenic nitroso bile acids. On this background duodenal juice was analyzed for bacterial contents, the spectrum of bile acids, and genotoxicity. Methods: Sprague-Dawley rats were operated with esophagojejunostomy to produce duodeno-esophageal reflux (n=15). At the time of surgery, after 2, and 6 weeks, duodenal contents were aspirated and analyzed immediately for bacterial contents with standard techniques. Tandem mass spectrometry was applied for the detection of bile acids and their respective nitroso derivatives. Genotoxicity was assessed with the micronucleus test measuring toxicity by a decrease of the percentage of binuclear cells (Bnc) and genotoxicity by the prevalence of micronuclei (Mn). Results: In all pre- and postoperative samples (15/15) taurocholic acid (TCA) and glycocholic acid (GCA) as predominating conjugates were detected. Following surgery bacterial overgrowth with fecal bacteria in concentrations up to 107 per ml was present in all animals. However, even selective reaction monitoring failed to demonstrate the presence of any nitroso- TCA or nitroso-GCA (detection limit 0.1% of the concentration of TCA). The table summarizes the results of the micronucleus test. Conclusions: Tumorigenesis of esophageal adenocarcinoma in the rodent model could not be linked to a specific carcinogen, especially not to nitroso bile acids. Duodenal juice was toxic, but not genotoxic. Chronic inflammation is likely to be the relevant mecha|nism of carcinogenesis by duodenogastric reflux. |
