In vitro studies indicate that nitrosation in acid stomach will be maximal at gastroesophageal (GO) junction

BACKGROUND: Nitrate absorbed from the GIT is secreted in saliva and converted to nitrite by buccal bacteria. Saliva is the main source of nitrite entering the acid stomach. Saliva also contains thiocyanate, a catalyst of nitrosation reactions. Ascorbic acid (AA) secreted in acidic gastric juice prevents the nitrite reacting with secondary amines to form nitrosoamines by converting it to nitric oxide (NO); in the process AA is oxidized to dehydroascorbic acid (DHA). AIMS AND METHODS: To study nitrosation under conditions simulating salivary delivery of nitrite into acidic gastric juice following a meal containing 2mmol nitrate (equivalent to salad portion). RESULTS: The delivery of nitrite (at a rate simulating salivary delivery) into HCL containing thiocyanate (Immol/I) resulted in nitrosation of morpholine to nitrosomorpholine. The rate of nitrosation was greatest at pH 2.5. Infusion of AA at a rate simulating its gastric secretion failed to prevent nitrosation. The ineffectiveness of the AA was due to oxygen in atmospheric air increasing by tenfold the amount of AA required to remove the nitrite by converting it all to NO. This increased requirement of AA was due to the NO combining with the oxygen to reform nitrite. Further studies showed that the rate of consumption of AA by acidified nitrite containing thiocyanate was extremely rapid in the presence of air with the nitrite consuming 5 times its molar equivalent of AA within 5 seconds. CONCLUSION: Air is swallowed along with nitrite and thiocyanate in saliva and will result in the rapid consumption of AA on entering the acid stomach and consequently uninhibited nitrosoamine formation. This will be maximal at the GO junction where the reactants first meet and may explain the high incidence of mutagenesis at this anatomical site.