Studies in gastric carcinogenesis. III. The kinetics of nitrosation of gastric-juice components in vitro and their implications for the in vivo formation of N-nitroso compounds in normal and in hypochlorhydric populations.

Fasting human gastric juice was treated in vitro, at pH 2-7 and 37 degrees C for 2 h, with 5-100 microM sodium nitrite. Under these conditions (which simulated those occurring in vivo in normal or hypochlorhydric individuals), the formation of total N-nitroso compounds had the following characteristics: (i) it increased greatly at pH less than 3; (ii) it showed first-order dependence on nitrite concentration; (iii) it was faster at pH 7 than at pH 5. These observations are compatible with the N-nitroso compounds formed by the interaction of nitrite with gastric juice being N-nitrosamides or related compounds. Furthermore, based on the results of this study, it is suggested that in order for hypochlorhydria to give rise to increased formation of N-nitroso compounds in the stomach, it would be necessary for it to be accompanied by a greater than 5- to 10-fold increase in gastric nitrite concentration relative to that found in the normal population, a condition which is not necessarily fulfilled in all hypochlorhydric individuals or populations. The implications of this conclusion for the assessment of the role on gastric N-nitroso compounds in the etiology of gastric cancer are discussed.