Hypothesis on the relationship between gastric cancer and intragastric nitrosation: N-nitrosamines in gastric juice of subjects from a high-risk area for gastric cancer and the inhibition of N-nitrosamine formation by fruit juices.

The concentration of N-nitrosamines (NNA) in gastric juice was determined as an indicator of intragastric N-nitrosation in 85 subjects from a high-risk area for gastric cancer (GC) to examine the relationship between N-nitroso compounds (NOC), pH and intragastric lesions under strictly controlled conditions. Mean gastric pH in subjects with GC or dysplasia (Group GD, 5.0 +/- 2.7) was higher than that from subjects with intestinal metaplasia (Group IM, 3.8 +/- 2.1, p = 0.068) and significantly higher than in those with normal mucosa or superficial gastritis (Group NS, 2.6 +/- 1.9, p < 0.001). No significant difference (p > 0.1) was found in total NNA concentrations between the three groups (GD 1.81 +/- 1.05 micrograms/l, IM 1.46 +/- 0.79 micrograms/l, NS 1.56 +/- 1.38 micrograms/l). However, two obvious peaks of nitrosation were observed at pH ranges of < 2.0 and 5.5-7.5. These observations were confirmed by using the N-nitrosoproline test in the same subjects under the same conditions (r = 0.772, p < 0.05). These results indicate that intragastric nitrosation can occur in both acidic and nearly neutral conditions. The first peak is related to acid-catalysed nitrosation (ACN) and the second is related to biologically catalysed nitrosation (BCN). According to these and other published results the hypothesis that there are two basic mechanisms, ACN and BCN, for intragastric N-nitrosation in humans is explored. Gastric carcinogenesis in high-risk areas is more likely to be related to intragastric NOC formed by ACN, compared to low-risk areas where it is more likely to be related to intragastric NOC formed by BCN. Fruit juices and orange peel significantly inhibited intragastric nitrosation by both ACN and BCN.