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

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.

Erratum: Salt tea consumption and esophageal cancer: A possible role of alkaline beverages in esophageal carcinogenesis

“…The frequent consumption of hot salt tea is shown to result in exceptionally high exposure to methylamine (1,200 μg day −1 ), ethylamine (14,320 μg day −1 ), dimethylamine (150 μg day −1 ), diethylamine (400 μg day −1 ), and nitrate (up to 23 μg day −1 ) . These amines are among known nitrosatable precursors in human diet that can get transformed to N‐nitrosamines under appropriate gastric conditions (pH, nitrite, presence of nitrosation catalysis) or in achlorhydric stomach (mediated by nitrate—reducing bacteria) . Because of rapid absorption and metabolism, the exact quantification of N‐nitrosamines in stomach is not possible.…”

Inducible nitric oxide synthase activity induced by sodium chloride solution prolongs luminal pH elevation in rat and mouse stomachs

“…NO produced by iNOS is known to form nitroso compounds (NOC), potent carcinogens, endogenously produced under inflammatory conditions 18 . Elevated luminal pH levels and the growth of bacteria have also been reported to enhance the formation of NOC, leading to gastric carcinogenesis 40 . Recently, we found mutagenic activation of carcinogens by microsomes prepared from gastric mucosa with intestinal metaplasia 41 .…”

Chemoprevention in Barrett’s Esophagus

“…19 Nitrates are concentrated by the salivary glands and secreted into the mouth, 20 where oral microbes reduce these nitrates to nitrites. 20 Moreover, achlorhydria induced by PPI use leads to overgrowth of nitrate-reducing bacteria in the stomach, 19,21 and these bacteria convert dietary nitrate to nitrite. Contents of gastroduodenal reflux in the lower esophagus change these nitrites to nitrous acid and eventually to nitric oxide.…”