Fat transforms ascorbic acid from inhibiting to promoting acid-catalysed N-nitrosation (original) (raw)
Fat transforms ascorbic acid from inhibiting to promoting acid-catalysed _N-_nitrosation
- E Combet1,
- S Paterson1,
- K Iijima1,
- J Winter1,
- W Mullen2,
- A Crozier2,
- T Preston3,
- K E L McColl1
- 1
Division of Cardiovascular and Medical Sciences, Western Infirmary, University of Glasgow, Glasgow, Scotland - 2
Plant Products and Human Nutrition Group, Division of Environmental and Evolutionary Biology, Graham Kerr Building, University of Glasgow, Glasgow, Scotland - 3
Stable Isotope Biochemistry Laboratory, SUERC, East Kilbride, Scotland - Professor Kenneth E L McColl, Medical Sciences, Western Infirmary, Glasgow G11 6NT, Scotland, UK; k.e.l.mccoll{at}clinmed.gla.ac.uk
Abstract
Background: The major potential site of acid nitrosation is the proximal stomach, an anatomical site prone to a rising incidence of metaplasia and adenocarcinoma. Nitrite, a pre-carcinogen present in saliva, can be converted to nitrosating species and _N-_nitroso compounds by acidification at low gastric pH in the presence of thiocyanate.
Aims: To assess the effect of lipid and ascorbic acid on the nitrosative chemistry under conditions simulating the human proximal stomach.
Methods: The nitrosative chemistry was modelled in vitro by measuring the nitrosation of four secondary amines under conditions simulating the proximal stomach. The _N-_nitrosamines formed were measured by gas chromatography–ion-trap tandem mass spectrometry, while nitric oxide and oxygen levels were measured amperometrically.
Results: In absence of lipid, nitrosative stress was inhibited by ascorbic acid through conversion of nitrosating species to nitric oxide. Addition of ascorbic acid reduced the amount of _N-_nitrosodimethylamine formed by fivefold, _N-_nitrosomorpholine by >1000-fold, and totally prevented the formation of _N-_nitrosodiethylamine and _N-_nitrosopiperidine. In contrast, when 10% lipid was present, ascorbic acid increased the amount of _N-_nitrosodimethylamine, _N-_nitrosodiethylamine and _N-_nitrosopiperidine formed by approximately 8-, 60- and 140-fold, respectively, compared with absence of ascorbic acid.
Conclusion: The presence of lipid converts ascorbic acid from inhibiting to promoting acid nitrosation. This may be explained by nitric oxide, formed by ascorbic acid in the aqueous phase, being able to regenerate nitrosating species by reacting with oxygen in the lipid phase.
- cancer
- diet, gastro-oesophageal junction, nitrite
- nitrosation
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Gut 2007; 56 1645-1645 Published Online First: 12 Nov 2007.