Bacterial formation of N-nitroso compounds from administered precursors in the rat stomach after omeprazole-induced achlorhydria

Carcinogenesis. 1991 Mar;12(3):435-9. doi: 10.1093/carcin/12.3.435.

Abstract

The role of bacteria in catalysing intragastric formation of N-nitrosothiazolidine-4-carboxylic acid and N-nitrosomorpholine was investigated in a rat model of omeprazole-induced achlorhydria. Omeprazole-treated rats gavaged with nitrosation-proficient bacteria were treated with nitrosamines and/or precursors and compared to control animals that received no omeprazole treatment/no bacteria. Rats given thiazolidine-4-carboxylic acid, nitrate and 10(11) cells of Escherichia coli, had a five times higher endogenous formation of N-nitrosothiazolidine-4-carboxylic acid as compared to controls. Endogenous formation of N-nitrosomorpholine was quantified by measuring its urinary metabolite N-nitroso-(2-hydroxyethyl)glycine; when rats were given morpholine and nitrite together with E. coli or Pseudomonas aeruginosa endogenous N-nitrosomorpholine formation was increased approximately 2.5-fold as compared to controls. In the same experiment, a higher excretion of unchanged N-nitrosomorpholine was also observed in omeprazole-treated rats receiving bacteria as compared to controls. Rats given morpholine, nitrate and E. coli or P. aeruginosa, excreted three times higher levels of N-nitrosomorpholine as compared to controls. These results conclusively demonstrate that nitrosation-proficient bacteria are capable of increasing intragastric formation of N-nitrosothiazolidine-4-carboxylic acid and N-nitrosomorpholine. These N-nitrosamines are formed from nitrate (or nitrite) and the respective amino precursor via reduction of nitrate into nitrite and bacterial nitrosation catalysis.

MeSH terms

  • Achlorhydria / chemically induced
  • Achlorhydria / metabolism*
  • Achlorhydria / physiopathology
  • Animals
  • Escherichia coli / metabolism*
  • Gastric Mucosa / metabolism
  • Hydrogen-Ion Concentration
  • Male
  • Morpholines / metabolism
  • Nitrosamines / metabolism*
  • Nitroso Compounds / metabolism*
  • Omeprazole / pharmacology*
  • Pseudomonas aeruginosa / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Stomach / drug effects
  • Stomach / microbiology*
  • Thiazoles / metabolism*
  • Thiazolidines

Substances

  • Morpholines
  • Nitrosamines
  • Nitroso Compounds
  • Thiazoles
  • Thiazolidines
  • N-nitrosomorpholine
  • N-nitrosothiazolidine-4-carboxylic acid
  • morpholine
  • thiazolidine-4-carboxylic acid
  • nitrosoproline
  • Omeprazole