The effect of intra-gastric acidity and flora on the concentration of N-nitroso compounds in the stomach

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Abstract
Correa's hypothesis proposes that gastric carcinogenesis is due to atrophic gastritis and hypochlorhydria which permit gastric bacterial colonization, the reduction of dietary nitrates to nitrites and the formation of potentially carcinogenic N -nitroso compounds (NOCs). To test the hypothesis that omeprazole-induced hypochlorhydria is associated with increased intra-gastric concentrations of nitrate-reducing bacteria (NRB), nitrites and NOCs. Single-blind study in healthy volunteers. Fourteen healthy subjects (seven female, mean age 24 years), free of Helicobacter pylori infection, received a one-week course of placebo followed by a two-week course of omeprazole, 20 mg daily. Fasted gastric samples, aspirated using a sterile double-lumen nasogastric tube at the end of the 1st week (placebo) and the 2nd and 3rd weeks (omeprazole), were cultured aerobically and anaerobically; gastric pH and intra-gastric concentrations of nitrates, nitrites and NOCs were also determined. After weeks 1, 2 and 3, the intra-gastric concentrations of nitrate-reducing bacteria exceeded 105 colony-forming units (c.f.u.)/ml in 3, 7 and 9 subjects, respectively ( P > 0.05). A gastric pH greater than 4.0 was associated with increased NRB ( P < 0.05); however, neither increased gastric pH nor increased NRB, alone or in combination, was associated with increased intra-gastric concentrations of nitrites or NOCs ( P > 0.05). A two-week increase in gastric pH in healthy, H. pylori -negative subjects was associated with increased intra-gastric concentrations of nitrate-reducing bacteria but not of nitrites or N -nitroso compounds. These data suggest that reduced gastric acid secretion is not a necessary precursor to the formation of carcinogenic N -nitroso compounds and that other mechanisms should be invoked to explain gastric carcinogenesis. Eur J Gastroenterol Hepatol 12:165-173 © 2000 Lippincott Williams & Wilkins European Journal of Gastroenterology & Hepatology 2000, 12:165-173

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