Relevance of nitrosamines to human cancer.

It is now about three decades since the hepatocarcinogenic effect of N-nitrosodimethylamine (NDMA)* was demonstrated in rats (1) and the suggestion was made that N-nitrosamines can be formed following nitrosation of various amines (2). Direct proof that such nitrosation reactions can occur was provided by Ender et al. (3) who identified NDMA in nitrite preserved fish-meal, and by Sander and Seif (4) who demonstrated the formation in vivo of a nitrosamine in the acidic conditions of the human stomach. Since then, because of the potent carcinogenicity, wide environmental occurrence and easy formation of nitrosamines, considerable efforts have gone into determining their levels in the external and internal human environment, and attempts have been made to assess exposure and to correlate it with human cancer at specific sites. Fundamental research into molecular and cellular mechanisms of carcinogenesis has also concentrated on N-nitroso compounds (NOC), to find out why and how this class of carcinogens produces tumours in up to 40 animal species (5,6) and displays remarkable species, organ and cell specificity (7—11) and a wide variety of genetic effects (12,13).