Mechanisms potentially responsible for formation, activation, and detoxication of carcinogenic N-nitroso compounds in the human body are under intensive investigation. The bifunctional amine, piperazine, which is used as an anthelmintic in humans, has been shown to react with nitrite with remarkable facility under catalysis by certain iron complexes. The results suggest that similar catalysis by biological iron compounds may be responsible for some endogenous formation of nitrosamines in vivo. Activation studies have revealed that many volatile anesthetics, including ether, act as competitive inhibitors of nitrosamine metabolism and that N-nitrosomethylethylamine can 2-hydroxyethylate as well as methylate and ethylate DNA. The latter result was predicted on the basis of deuterium isotope effect investigations. The deuterium isotope effect on conversion of formaldehyde and formate to carbon dioxide--one-carbon intermediates in the oxidation of N-nitrosodimethylethylamine (NDMA)--has been found to be negligible. The extent of denitrosation, a potentially very important detoxication route for NDMA, has been estimated in vivo from urinary methylamine excretion data. Refinements of destruction methods for carcinogenic N-nitroso compounds have been introduced and several salts of nitrosamines with strong acids have been prepared.
