Cancer Letters

Cancer Letters

Volume 124, Issue 2, 27 February 1998, Pages 119-125
Cancer Letters

Volatile N-nitrosamines in gastric juice of patients with various conditions of the gastrointestinal tract determined by gas chromatography–mass spectrometry and related to intragastric pH and nitrate and nitrite levels

https://doi.org/10.1016/S0304-3835(97)00467-9Get rights and content

Abstract

Gastric juice samples of 71 patients undergoing upper gastrointestinal endoscopy were collected as well as saliva samples from 40 of these patients. Age, sex, endoscopic diagnosis and medication were recorded. The gastric juice samples were analyzed for the presence and quantity of individual volatile N-nitrosamines, which were detected by gas chromatography–mass spectrometry, without prior derivatization. The samples were screened for eight nitrosamines, i.e. N-nitrosodimethylamine, N-nitrosoethylmethylamine, N-nitrosodiethylamine, N-nitrosodi-n-propylamine, N-nitrosodi-n-butylamine, N-nitrosopyrrolidine, N-nitrosopiperidine and N-nitrosomorpholine. The pH of the fresh gastric juice as well as nitrate and nitrite levels of gastric juice and saliva were determined. The mean total level of volatile N-nitrosamines in gastric juice was found to be 4.84 nmol/l (range 0–17.7 nmol/l). The main N-nitrosamines found were N-nitrosodiethylamine (mean concentration 3.1 nmol/l), N-nitrosodimethylamine (mean concentration 0.90 nmol/l) and N-nitrosopyrrolidine (mean concentration 0.38 nmol/l). Significant correlations between mean intragastric pH values and mean N-nitrosodi-n-butylamine level (P=0.005) and total volatile N-nitrosamine contents (P=0.009) were observed.

Introduction

During the past 2 decades various studies 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22and reviews 23, 24, 25, 26, 27, 28, 29, 30, 31concerning the endogenous formation of N-nitroso compounds (NOC) in gastric juice in relation to gastric carcinogenesis have been published. In most of these studies, apparent total N-nitroso compounds were determined by chemical denitrosation to form NO and thermal energy analysis (TEA) 1, 2, 3, 4, 5. These data have been related to gastric pathology 5, 6, 7, 9, gastric nitrate and nitrite concentrations 4, 5, 6, 7, 8, 22, pH 3, 4, 5, 6, 7, 8, 12, bacterial overgrowth 6, 7, 10, 11, medication 3, 8, 9, 10, 32and salivary [33]and urinary nitrate, nitrite and NOC concentrations 12, 13, 14, 34. Other papers describe the nitrosation of specific amino compounds, such as proline, as a model for endogenous nitrosation 15, 16, 17, 18, 30, 35or the inhibition of such reactions by scavengers 22, 23, 36, 37, e.g. ascorbic acid. Epidemiological research in gastric cancer has recently been reviewed [24], with emphasis on the role of nitrate burden and endogenous nitrosation reactions.

The availability of capillary gas chromatography in combination with high sensitivity and when necessary, high resolution mass spectrometry, enables the accurate and sensitive detection and determination of individual volatile N-nitrosamines (NAms) [38]. Correlation of the concentration of NAms in the gastric juice of subjects with various clinical conditions of the gastrointestinal tract with other intragastric parameters and with medical history might provide an insight into the formation of individual NAms as well as into their clinical relevance. Therefore, we screened the volatile NAm content of the gastric juice of 71 patients and compared the results with gastric pH and with nitrate and nitrite levels in saliva and gastric juice.

Section snippets

Patients

Gastric juice samples were obtained endoscopically from 71 patients with various upper abdominal complaints who visited the Endoscopy Department of the University Hospital Maastricht. Saliva samples (n=40) were also collected at the same time from some of these patients. At the time the gastric juice and saliva samples were collected, the patients had fasted for at least 12 h. For men (n=39) and women (n=32) the mean age was 56 years (range 27–85 years) and 55 years (range 17–85 years),

Results and discussion

The concentrations of the individual NAms in the gastric juice samples were determined and mean values are given in Table 1. The main volatile NAm detected in gastric juice appeared to be NDEA, which represented approximately 70% of the total volatile NAms found. No influence of sex and age on the individual and total volatile NAm content and on gastric juice pH could be detected.

The mean nitrate and nitrite concentrations in saliva and in gastric juice are given in Table 2. The concentrations

Conclusions

Capillary GC-MS proved to be a useful tool for the detection and quantitation of individual volatile NAms in gastric juice. High resolution mass spectrometry was used to confirm the elemental composition of the compounds detected. In combination with the retention time of these compounds, this enables a reliable determination of their identity. The levels of the individual NAm contents appear to be subject to a rather strong interindividual variance. Nevertheless, the data for volatile NAms

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