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© 1990 Oxford University Press

research-article

Quantitative estimates ofN-nitrosotrimethylurea formation in the porcine stomach

Chris M. Maragos, Joseph H. Hotchkiss 1 and Susan L. Fubini

Institute for Comparative aral Environmental Toxicolog and College of Veterinany Medicine, Stocking Hall, Cornell University Ithaca, NY 14853, USA

1To whom correspondence should be addressed

Gastric formation of N-nitrosotrimethylurea (NTMU) was quantified by repeated sampling of the gastric contents of full-sized fistulated pigs after the addition of 250 µmol trimethylurea (TMU) and 25–125 µmol nitrite. Maximum gastric nitrite concentration was 100–500 µM based on the gastric volume and amount ofadded nitrite, which is within the range reported in human gastric contents. The total amount of NTMU formed over time wasquantified by estimating both the NTMU concentration and gastric volume using multiple additions of polyethylene glycol. Admini stration of 25 µmol of nitrite resulted in the formation of 320 nmol of NTMU. The total amount of NTMU formedwas linearly related to nitrite dose. Conversion of nitrite to NTMU was of the order of 1–3%. Potassium thiocyanate (200–2000 µmol) had no effect on NTMU formation when given immediately preceding 75 µmol nitrite. Ascorbic acid at 225 and 341 µmol (0.66 and 1.0 of the recommended dietary allowance) inhibited nitrosation ofTMU by an average of 54 and 84%. A pig with an average gastric p of 1.9 formed 4.5-fold more NTMU than did a secondpig at pH 4.8. These results suggest that low micromolar amounts of N-nitrosoureas can be formed in the normal stomach when nitrite is conswned in amounts to which humans are commonly exposed.


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