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Effect of Gastric Secretion on Penetration of N-3H-Methyl-N-nitro-N-nitrosoguanidine into Gastric Mucosa of Rats

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Abstract

Clinical conditions with low gastric acidsecretion have been associated with increased risk ofgastric cancer. There has also been concern aboutgastric acid inhibition and N-nitroso compound formation in the stomach. This study investigates theeffect of gastric acid secretion on the penetration ofN-3H-methyl-N-nitro-N-nitrosoguanidine, anN-nitroso compound and gastric carcinogen, into thegastric mucosa of rats. Gastric acid secretion wasstimulated by pentagastrin (40 μg/kg/hr) andinhibited by omeprazole (40 mumol/kg) before mucosalexposure toN-3H-methyl-N-nitro-N-nitrosoguanidine.Penetration of the carcinogen was evaluated by lightmicroscopic identification of cells in the S-phaselabeled withN-3Hmethyl-N-nitro-N-nitrosoguanidine. Thispopulation of double-labeled cells is considered at risk fromN3-methyl-N-nitro-N-nitrosoguanidine-inducedcarcinogenesis. The percentage of double-labeled cellswas significantly higher in antrum than in corpus mucosa(P < 0.0001). Stimulation or inhibition of gastric acid secretion did notaffect the penetration of N-3H-methyl-N-nitro-N-nitrosoguanidine in antrum or corpusmucosa. We conclude that modulation of gastric acidsecretion does not affect the penetration of the carcinogeninto the gastric mucosa nor does it explain thedifferent penetration of the carcinogen into corpus andantrum mucosa.

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Authors
  1. Kjell K. Ovrebo
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  2. Halfdan Sorbye
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  3. Steinar Kvinnsland
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  4. Ketil Grong
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  5. Knut Svanes
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Ovrebo, K.K., Sorbye, H., Kvinnsland, S. et al. Effect of Gastric Secretion on Penetration of N-3H-Methyl-N-nitro-N-nitrosoguanidine into Gastric Mucosa of Rats. Dig Dis Sci 43, 2012–2020 (1998). https://doi.org/10.1023/A:1018898928870

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