Quantitative estimates ofN-nitrosotrimethylurea formation in the porcine stomach

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Abstract
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.