Studies in the guinea-pig stomach on the formation of N-nitrosomethylurea, from methylurea and sodium nitrite, and its disappearance.

The formation of N-nitrosomethylurea (NMU) from methylurea (MU) and sodium nitrite in the guinea-pig stomach and the disappearance of NMU from the stomach were studied using a previously described method for NMU determination (Yamamoto et al. Fd Chem. Toxic. 1986, 24, 247). Guinea-pigs were used since they have only glandular stomachs and the pH of the gastric juice (1-2) is similar to that of humans. NMU was relatively stable in the isolated gastric contents of this species. When 2 mumol NMU was injected into the pylorus-ligated stomach of fasting guinea-pigs, about 50 and 37% of the NMU remained at 20 and 30 min, respectively. Some 19 and 42% remained 30 min after NMU was given orally by stomach tube to fasting and feeding guinea-pigs, respectively. NMU was detected in most blood samples irrespective of the administration procedure, but it disappeared rapidly from the blood after iv injection. Nitrite disappeared rapidly from the pylorus-ligated stomach, residual nitrite being less than 20% of the dose in 2.5 min. when 7.5 mumol MU and 15 mumol NaNO2 were co-injected into the ligated stomach, 3.1 mumol NMU was detected 10 min after the injection, followed by a gradual decrease. When MU and NaNO2 were given orally to the animals, 0.7-1.0 mumol NMU was detected in the stomach 10 min after the treatment. Thus NMU was shown to be formed readily in the stomach of the guinea-pig and to be absorbed from the stomach into the blood.