In vivo nitrosoproline formation and other risk factors in Costa Rican children from high- and low-risk areas for gastric cancer.

The hypothesis that intragastric synthesis of N-nitroso compounds (NOC) in early life could play a role in gastric carcinogenesis was tested by applying the N-nitrosoproline (NPRO) test to about 50 children living in high- and low-risk areas for stomach cancer in Costa Rica. The median values of excretion of NPRO and the sum of three nitrosamino acids (micrograms/12 h urine) were 10-20% of those in adults from other geographical high-risk areas for stomach cancer. The urinary NPRO level after proline intake was higher in children from the high-risk area (P < 0.04) and markedly reduced after ingestion of ascorbic acid together with proline (P < 0.05). NPRO levels on the day of proline intake were highly correlated with levels of nitrate excretion (P < 0.001). Mean levels of total NOC in an aqueous (pH 2) extract of cooked beans from the high- and low-risk areas were similar. Acid-catalyzed nitrosation of the extract increased the total NOC concentration up to 1000-fold, but there was no difference between samples from the two areas. About 10% of bean extracts from both areas showed weak direct-acting genotoxicity in Escherichia coli; after acid-catalyzed nitrosation, all samples were genotoxic at similar levels. The diet of children in the low-risk area satisfied recommended levels of intake of energy and most nutrients except riboflavin and retinol equivalents. Diets from the high-risk area were deficient in energy intake and all nutrients except protein and vitamin C.(ABSTRACT TRUNCATED AT 250 WORDS)

Mutagens, N-nitroso compounds and their precursors in gastric juice from patients with and without precancerous lesions of the stomach.

This study examined whether elevated risk of gastric cancer is associated with high levels of total N-nitroso compounds (NOC), their precursors and nitrosation-dependent genotoxins in gastric juice (GJ). An improved method for quantifying total NOC was used and genotoxicity was assayed in E. coli. Results from patients (n = 210) with or without precancerous lesions of the stomach and living in three areas with up to 8-fold variations in gastric cancer risk (U.K., France, Colombia) were compared. The level of nitrite (range < 1-472 mumol/l) was found to increase with the pH of GJ from the three countries and was dependent on country of collection. The levels of NOC (range: < or = 0.01-8.0 mumol/l) in GJ were not affected by stomach histology and country of collection. NOC levels increased linearly with nitrite concentrations, but the slope of the regression line was greater for acidic GJ (pH < or = 4). These data together suggest that chemical nitrosation contributes at least as much as other nitrosation pathways to the intragastric formation of NOC. Acid-catalysed nitrosation of GJ in vitro increased the NOC concentration (range: 7-1332 mumol/l) up to several 1000-fold but this increase was not predictive of gastric cancer risk either by country or by stomach histology. After acid-catalysed nitrosation, direct genotoxicity (SOS-inducing potency) was significantly higher in GJ with original pH > 4 and highest in samples from Colombia. The results (a) provide no support that intragastric total NOC levels are elevated in subjects with precancerous stomach lesions or living in a high risk area for stomach cancer; (b) confirm that a high nitrite level and elevated pH in GJ are strongly associated, the level of nitrite being associated with precancerous stomach conditions only in Colombia; (c) reveal the presence of precursor compounds in GJ, that after nitrosation yield direct mutagens that probably contain NOC and other substances. As their concentrations were significantly higher in achlorhydric subjects and highest in Colombian patients, these data together provide support for a role of intragastrically formed nitrite-derived direct mutagens in gastric cancer aetiology.

Exposure to N-nitrosamines and other risk factors for gastric cancer in Costa Rican children.

The hypothesis that endogenous chemical nitrosation in the normal stomach in early life could play a crucial role in inducing chronic atrophic gastritis/intestinal metaplasia in later life was tested by applying the N-nitrosoproline (NPRO) test to 12-h urine samples from about 50 children (aged 8-14 years) living in high- and low-risk areas for stomach cancer. The median values of NPRO and the sum of four nitrosamino acids analysed were 0.28-0.84 micrograms/12 h and 0.75-1.75 micrograms/12 h, respectively. The NPRO level after proline intake was significantly higher in children from a high-risk area than in those from a low-risk area (p less than 0.04), and markedly reduced after ingestion of ascorbic acid and proline (p less than 0.05). Urinary nitrate level was lower than that of adults. NPRO levels on the day of proline intake, however, correlated well with nitrate levels (p less than 0.001), indicating that children in a high-risk area in Costa Rica have high endogenous nitrosation potential. Blood samples were also collected from about 300 children (aged 7-20 years) and analysed for antibodies against Campylobacter pylori, a suspected gastritis-causing bacteria. About 71% of children in both high- and low-risk areas for stomach cancer had antibodies. In addition, raw and cooked beans, which are consumed very frequently in Costa Rica, were collected from families in both areas and analysed for levels of nitrite/nitrate, total N-nitroso compounds and genotoxicity in the SOS chromotest.(ABSTRACT TRUNCATED AT 250 WORDS)