Bacterial formation of N-nitroso compounds from administered precursors in the rat stomach after omeprazole-induced achlorhydria.
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.
Calmels
S
S
International Agency for Research on Cancer, Lyon, France.
Béréziat
J C
JC
Ohshima
H
H
Bartsch
H
H
D000126:Achlorhydria / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D004926:Escherichia coli / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008297:Male; D009025:Morpholines / Q000378:metabolism; D009602:Nitrosamines / Q000378:metabolism*; D009603:Nitroso Compounds / Q000378:metabolism*; D009853:Omeprazole / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000187:drug effects / Q000382:microbiology*; D013844:Thiazoles / Q000378:metabolism*; D053778:Thiazolidines
D009025:Morpholines; D009602:Nitrosamines; D009603:Nitroso Compounds; D013844:Thiazoles; D053778:Thiazolidines; C002741:N-nitrosomorpholine; C040387:N-nitrosothiazolidine-4-carboxylic acid; C037574:morpholine; C003438:thiazolidine-4-carboxylic acid; C010259:nitrosoproline; D009853:Omeprazole