Quantitative estimates of N-nitrosotrimethylurea formation in the porcine stomach

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