N‐nitroso compounds: Their chemical and in vivo formation and possible importance as environmental carcinogens

Abstract

Brief reviews are presented on the occurrence of N‐nitroso (NNO) compounds, the chemistry and kinetics of NNO compound formation from nitrite and amines or amides, the in vivo formation of these compounds (as detected by tumor induction) on feeding nitrite with amines or amides to rodents, and the carcinogenicity for rats of some new nitrosamides. The possible human hazard caused by exposure to specific readily nitrosated compounds is reviewed. Whether NNO compounds might be causing human cancer of various organs (e.g., pancreatic, nasopharyngeal, and esophageal cancer) is discussed. Some of our results on [³H] thymidine incorporation in the rat esophageal epithelium are presented. Nitrosamines that cause esophageal cancer in rats were found to inhibit [³H] thymidine incorporation, both in vivo and in vitro, when esophagi were incubated with nitrosamines. With reference to the hypothesis that human gastric cancer is caused by nitrosamides (e.g., nitrosoureas), certain correlations were examined between gastric cancer and environmental exposure to nitrate, nitrite, and nitrosatable amides. In studies from our laboratory, dried, salted fish, which was treated with excess nitrite at pH 1 and then “denitrosated” at pH 0, yielded 16 mg methylurea/kg fish, possibly derived from methylguanidine.