N-nitroso Compounds In Gastric Juice Research Articles

Gastric juice nitrite and vitamin C in patients with gastric cancer and atrophic gastritis: is low acidity solely responsible for cancer risk?

N-nitroso compounds are carcinogens formed from nitrite, a process that is inhibited by vitamin C in gastric juice. Helicobacter pylori infection has been reported to increase nitrite and decrease vitamin C in gastric juice. Therefore, susceptibility to gastric cancer in H. pylori-infected patients may be derived from increased N-nitroso compounds in gastric juice. However, most H. pylori-infected patients do not develop gastric cancer. To investigate additional factors that may affect susceptibility to gastric cancer, we compared nitrite and vitamin C levels in gastric juice from H. pylori-infected patients with and without gastric cancer. Serum and gastric juice were obtained from 95 patients undergoing diagnostic endoscopy, including those with normal findings, duodenal ulcer, gastric ulcer, atrophic gastritis and gastric cancer. Serum was analysed for H. pylori antibody, nitrate and nitrite, gastrin and pepsinogens; gastric juice was analysed for pH, nitrite and vitamin C. pH and nitrite levels were increased and vitamin C levels decreased in the gastric juice of patients with atrophic gastritis and gastric cancer compared with other patients. However, in patients with a similar gastric acidity (pH 5-8), nitrite concentrations in the gastric juice were significantly higher and vitamin C levels significantly lower in patients with gastric cancer than in those with atrophic gastritis. Although hypochlorhydria increases intraluminal nitrite and decreases intraluminal vitamin C, which increases the intraluminal formation of N-nitroso compounds, our results indicate that patients with gastric cancer may have additional factors that emphasize these changes.

Effect of omeprazole on intragastric bacterial counts, nitrates, nitrites, and N-nitroso compounds.

Previous studies have suggested that profound inhibition of gastric acid secretion may increase exposure to potentially carcinogenic N-nitroso compounds. The aim of this study was to find out if the proton pump inhibitor omeprazole (20 mg daily) is associated with increased concentrations of potentially carcinogenic N-nitroso compounds in gastric juice. The volume of gastric contents, number of bacteria, and concentrations of nitrates, nitrites, and N-nitroso compounds was determined in gastric aspirates obtained after an overnight fast in 14 healthy volunteers (7M:7F) after one week of treatment with placebo, and one and two weeks' treatment with omeprazole. Median bacterial concentrations were 1.0 x 10(4) (range 5.0 x 10(3)-5.0 x 10(6)) colony forming units (CFU)/ml after one weeks' treatment with placebo and increased significantly to 4.0 x 10(5) (0-3.3 x 10(7)) CFU/ml after two weeks' treatment with omeprazole (p < 0.05). A similar increase was seen in the concentration of nitrate reducing bacteria. There was no difference in the volume of gastric aspirates after treatment with omeprazole when compared with placebo (65 (29-155) ml v 42 (19-194) ml). The concentration of N-nitroso compounds was 0.13 (0-1.0) mumol/l after two weeks of omeprazole, which was not significantly different from that seen with placebo (0.15 (0-0.61) mumol/l). There was also no increase in the concentrations of nitrates or nitrites. It is concluded that omeprazole (20 mg once daily) for two weeks in healthy volunteers is associated with gastric bacterial proliferation but does not increase concentrations of N-nitroso compounds.

Instability of N-nitroso compounds in gastric juice and preliminary results from analyses of fresh samples by using an improved analytical method

Using an improved method for determination of total N-nitroso compounds (NOC), we examined the stability of those compounds in fresh gastric juice samples during storage and the effects of the addition of 2% sulphamic acid on NOC concentration in 212 samples. The NOC levels in fresh samples decreased very rapidly at -20 degrees C, especially during the first 24 hours of storage (P < 0.01), and nitrite concentration also showed a decreasing trend during storage. The addition of sulphamic acid significantly reduced NOC levels from 1.97 +/- 0.21 to 1.10 +/- 0.12 mumol/l (mean +/- SE, P < 0.01), especially in samples of initially high pH. However, in some individual samples (16.5%) the NOC levels actually increased by 14.1% (P < 0.01). The results from analysis of NOC in 212 fresh samples in relation to pH demonstrated two significantly higher peaks of NOC concentrations at intragastric pH ranges 1.1 to 2.99 (P < 0.05) and 6.0 to 7.9 (P < 0.01). There was a significant relationship between nitrite level and intragastric pH (r = 0.480, P < 0.01), the nitrite concentration increasing dramatically when the pH exceeded 6.0. The present study suggest that a major proportion of the unidentified NOC formed through intragastric nitrosation is labile NOC; if the true concentration of NOC is to be determined it is therefore essential to analyse fresh gastric juice samples directly after collection and without pretreatment. It will also be necessary to characterize those labile NOC in order to study further the mechanism of endogenous N-nitrosation in man and its relation to human carcinogenesis.

Analytical problems in the determination of N-nitroso compounds in gastric juice

Gastric juices invariably contain nitrate and, those with pH values in excess of about 4 viable bacteria capable of reducing it to nitrite. Nitrite also enters the gastric juice from the saliva in which its source is dietary nitrate. On entering the stomach, nitrite either interacts with gastric amines, phenols, thiols, etc., or is absorbed or disproportionated to nitrate and nitric oxide, leaving a low resting concentration under acidic conditions. Thus, gastric components, such as phenols or thiols, can lead to other types of oxygenated nitrogen compounds than N-nitrosamines, N-nitrosamides, etc., such as C-nitroso or C-nitrophenols and S-nitrosothiols.

Urinary N-nitrosoproline excretion: a further evaluation of the nitrosamine hypothesis of gastric carcinogenesis in precancerous conditions.

Measurement of N-nitroso compounds in gastric juice by different methods has given conflicting results. In order to resolve this controversy, we have assessed endogenous nitrosation by the independent N-nitrosoproline excretion test in subjects who had previously undergone gastric juice analysis by one of these methods. Ten Polya gastrectomy, 10 pernicious anaemia and nine matched control subjects were fed 380 mg of nitrate in beetroot juice and 500 mg proline. N-nitrosoproline (N-Pro) synthesised intragastrically from these precursors, and quantitatively excreted by the kidneys, was measured in 24 hour urine samples (collection checked by creatinine clearance). N-Pro excretion (mean +/- SEM) was reduced (p less than 0.01) in pernicious anaemia (1.1 +/- 0.8 ng/day) compared with matched control (18.0 +/- 7.2 ng/day), and also tended to be lower (NS) in polya gastrectomy (3.2 +/- 2.3 ng/day). Twenty four hour intragastric pH was monitored on a separate occasion in 23 of the 29 subjects; 13 were hypoacidic (pH greater than 4 greater than 50% of 24 hours) and 10 were acidic. N-Pro yields were reduced (p less than 0.01) in the hypoacidic group (0.9 +/- 0.6 ng/day) compared with the acidic group (17.9 +/- 6.6 ng/day), and N-Pro was negatively associated with mean intragastric pH (tau = -0.53, p = 0.001). We conclude that endogenous synthesis of this specific N-nitroso compound is favoured by low rather than high pH. These results are concordant with those previously reported in gastric juice from the same subjects and suggest that nitrosation is chemically rather than bacterially mediated, contrary to the nitrosamine hypothesis of gastric carcinogenesis.

Improved group determination of total N-nitroso compounds in human gastric juice by chemical denitrosation and thermal energy analysis.

A procedure for the determination of total N-nitroso compounds (NOC) in human gastric juice was developed by modifying earlier methods. The gastric juice sample, treated with sulphamic acid to remove nitrite, is injected directly into refluxing ethyl acetate containing either acetic acid for determining thermo-and acetic acid labile thermal energy analyser (TEA) responsive compounds (TAC), or into hydrogen bromide for the determination of TAC and NOC. The nitric oxide (NO) levels released are measured using thermal energy analysis with chemiluminescence detection, and the difference between the two determinations represents the concentrations of NOC in gastric juice. This method is not affected by nitrate concentrations of up to 1000 µmol l–1.The method was found to be rapid, reproducible and sensitive (detection limit 0.02 µmol l–1 NOC), requiring only small volumes of gastric juice and no prior extraction. Because the difficulties arising from the system response to the denitrosating agent and variability of NO release by acetic acid from nitrite were eliminated, this improved method can more accurately distinguish NOC from most other TEA-responsive species. Suitable techniques for stabilising gastric juice samples from duodenal ulcer and atrophic gastritis patients and the influence of the time and storage conditions on NOC concentrations have been studied.

Evaluation of the Nitrosamine Hypothesis of Gastric Carcinogenesis in Man

Patients who had undergone a Billroth II gastrectomy (PG) or had pernicious anaemia (PA) and healthy matched control subjects (MC) participated in 24-h studies in which bacteria, nitrite and N-nitroso compounds (NOC) were measured in gastric juice and N-nitrosoproline (NPRO) in urine. Consistent with the nitrosamine hypothesis, intragastric levels of bacteria and nitrite were positively related to intragastric pH, but, contrary to the hypothesis, NOC in gastric juice and NPRO in urine were negatively related to intragastric pH.

Relation between gastric histology and gastric juice pH and nitrite and N-nitroso compound concentrations in the stomach after surgery for duodenal ulcer.

Formation of N-nitroso compounds in gastric juice has been implicated in the pathogenesis of cancer in the stomach after operation. Gastric juice was aspirated from 85 subjects: 23 were controls, 51 had previously undergone vagotomy and gastrojejunostomy, and 11 had previously undergone vagotomy and pyloroplasty. The gastric juice samples were analysed for pH, nitrite, and total N-nitroso compounds. A significant correlation was found between pH and nitrite concentration (p less than 0.01). No significant correlation was found between pH and total N-nitroso compound concentration or between nitrite and N-nitroso compound concentration. The vagotomy and gastrojejunostomy patients had higher pH values and higher concentrations of nitrites and N-nitroso compounds than controls (p = 0.01 in all cases). The 51 vagotomy and gastrojejunostomy patients also underwent endoscopy and biopsy. They were divided into three groups: group 1 (21 patients) had no intestinal metaplasia and no more than mild dysplasia; group 2 (20 patients) had intestinal metaplasia; and group 3 (10 patients) had moderate or severe dysplasia. Groups 2 and 3 both had higher pH values and higher nitrite concentrations than group 1 (p = 0.01 in all cases). There was no significant difference, however, between either group 2 or 3 and group 1 for total N-nitroso compound concentration. Since there was no simple linear relation between pH and N-nitroso compound concentration, it was concluded that formation of N-nitroso compounds at high pH was unlikely to be involved in the pathogenesis of gastric cancer in the hypochlorhydric stomach after operation. The relation between nitrite and histological abnormality was not associated with a similar relation between N-nitroso compounds and histological abnormality. It therefore appears that there is no simple relation between N-nitroso compounds and the pathogenesis of premalignant gastric mucosal changes.

Chemiluminometry of nitrite and N-nitroso compounds in gastric juice.

Journal Article Chemiluminometry of nitrite and N-nitroso compounds in gastric juice. Get access B Dang Vu, B Dang Vu Search for other works by this author on: Oxford Academic Google Scholar J L Paul, J L Paul Search for other works by this author on: Oxford Academic Google Scholar O G Ekindjian, O G Ekindjian Search for other works by this author on: Oxford Academic Google Scholar J Yonger, J Yonger Search for other works by this author on: Oxford Academic Google Scholar M Gaudric, M Gaudric Search for other works by this author on: Oxford Academic Google Scholar J Guerre J Guerre Search for other works by this author on: Oxford Academic Google Scholar Clinical Chemistry, Volume 29, Issue 10, 1 October 1983, Pages 1860–1861, https://doi.org/10.1093/clinchem/29.10.1860 Published: 01 October 1983