In vitro studies indicate that acid catalysed generation of N-nitrosocompounds from dietary nitrate will be maximal at the gastro-oesophageal junction and cardia

A. Moriya, J. Grant, C. Mowat, C. Williams, A. Carswell, T. Preston, S. Anderson, K Iijima, K. E. McColl

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

BACKGROUND: Dietary nitrate increases saliva nitrite levels and swallowed saliva is the main source of nitrite entering the acidic stomach. In acidic gastric juice, this nitrite can generate potentially carcinogenic N-nitrosocompounds. However, ascorbic acid secreted by the gastric mucosa can prevent nitrosation by converting the nitrite to nitric oxide.

METHODS: To study the potential for N-nitrosocompound formation in a model simulating salivary nitrite entering the acidic stomach and the ability of ascorbic acid to inhibit the process. Concentrations of ascorbic acid, total vitamin C, nitrite, nitrosomorpholine, oxygen and nitric oxide were monitored during the experiments.

RESULTS: The delivery of nitrite into HCl containing thiocyanate resulted in nitrosation of morpholine, with the rate of nitrosation being greatest at pH 2.5. Under anaerobic conditions, ascorbic acid converted the nitrite to nitric oxide and prevented nitrosation. However, in the presence of dissolved air, the ascorbic acid was ineffective at preventing nitrosation. This was due to the nitric oxide combining with oxygen to reform nitrite and this recycling of nitrite depleting the available ascorbic acid. Further studies indicated that the rate of consumption of ascorbic acid by nitrite added to natural human gastric juice (pH 1.5) was extremely rapid with 200 micromol/l nitrite consumed 500 micromol/l ascorbic acid within 10 s.

CONCLUSIONS: The rapid consumption of ascorbic acid in acidic gastric juice by nitrite in swallowed saliva indicates that the potential for acid nitrosation will be maximal at the GO junction and cardia where nitrite first encounters acidic gastric juice. The high incidence of mutagenesis and neoplasia at this anatomical location may be due to acid nitrosation arising from dietary nitrate.

Original languageEnglish
Pages (from-to)253-61
Number of pages9
JournalScandinavian Journal of Gastroenterology
Volume37
Issue number3
DOIs
Publication statusPublished - Mar 2002
Externally publishedYes

Keywords

  • Ascorbic Acid
  • Cardia cancer
  • Dietary Supplements
  • Drug Interactions
  • Esophagogastric Junction
  • Gastric Acid
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Models, Anatomic
  • Nitrates
  • Nitric Oxide
  • Nitrites
  • Nitroso Compounds
  • Saliva
  • Sensitivity and Specificity
  • Structure-Activity Relationship
  • Comparative Study
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Barrett Oesophagus
  • Intestinal metaplasia
  • Nitrosoamines
  • Oesophageal cancer
  • Vitamin C

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