Formation of N-Nitrosopiperidine from Piperidine and Sodium Nitrite in the Stomach and the Isolated Intestinal Loop of the Rat

Abstract

SINCE the first report of hepatic cancer in rats induced by nitrosodimethylamine¹, many nitrosamines have been shown to be carcinogenic in a wide range of organs of a wide variety of species^1–4. Following the suggestion that dietary nitrite and secondary amines might interact in the human stomach to form nitrosamines⁵, such synthesis has been demonstrated in vitro with animal and human gastric juice^6,7, and in vivo in laboratory animals⁷ and man⁸; nitrosamine synthesis was pH-dependent^7–10. Nitrosamines can also be synthesized in vitro at near neutral pH values in the presence of enteric bacteria¹¹; yields of nitrosamines are also determined by the basicity of the secondary amine. Presumptive evidence for in vivo synthesis of nitrosamines has been demonstrated by the induction of tumours in rats following chronic feeding of nitrite and secondary amines¹¹. We report here the synthesis of nitrosopiperidine in rats from nitrite and piperidine in gastric contents in vitro, and in the stomach and in the small intestine in vivo.