Bacterial formation of N-nitroso compounds in the rat stomach after omeprazole-induced achlorhydria.
N-Nitrosamine formation by bacteria in the achlorhydric stomach has been proposed as an important factor in the development of gastric cancer. Thus, the effect of the presence of bacteria in the stomach on endogenous nitrosation was investigated in rats given omeprazole (an inhibitor of gastric H+, K((+)-ATPase) which reduces gastric secretion sufficiently to allow survival of a bacterial suspension of Escherichia coli or Pseudomonas. When rats were given both thiazolidine 4-carboxylic acid and nitrate, greater endogenous nitrosamine formation was observed in rats receiving omeprazole and an E. coli suspension than in control or omeprazole-treated rats. A similar result was obtained when rats were given morpholine and nitrate. Since the endogenous formation of N-nitrosomorpholine (NMOR) can be evaluated more precisely from the levels of its urinary metabolites, N-nitrosohydroxyethylglycine (NHEG), the metabolism of NMOR was studied in omeprazole-treated rats. In this preliminary study, we showed that 60% of an oral dose of NMOR was excreted as NHEG, while in rats with a higher gastric pH 20% was excreted as NHEG. The amount of endogenously formed NMOR was increased in omeprazole-treated rats given morpholine and nitrite together with bacteria, and greater excretion of unchanged urinary NMOR was observed. Thus, as shown in this in-vivo model, bacteria efficiently reduce nitrate to nitrite and catalyse nitrosation, resulting in increased endogenous formation of N-nitroso compounds in the achlorhydric stomach.
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*; D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D008297:Male; D009602:Nitrosamines / Q000378:metabolism; D009603:Nitroso Compounds / Q000378:metabolism*; D009853:Omeprazole; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000382:microbiology; D013844:Thiazoles / Q000378:metabolism; D053778:Thiazolidines
D009602:Nitrosamines; D009603:Nitroso Compounds; D013844:Thiazoles; D053778:Thiazolidines; C002741:N-nitrosomorpholine; C040387:N-nitrosothiazolidine-4-carboxylic acid; D009853:Omeprazole