Carcinogenic nitrosamines: Free radical aspects of their action

NDMA and other nitrosamines may be activated into DNA binding intermediates by a cytochrome P450-dependent formation of α-nitrosamino radicals or photochemically. Within the catalytic site of cytochrome P450, these radical intermediates either combine with HO· to form α-hydroxynitrosamines or decompose into nitric oxide and N-methylformaldimine. In the presence of phosphate, mutagenic α-phosphonooxy derivatives are formed from radicals generated chemically/photochemically. Studies on lipid peroxidation, in vivo and in vitro, have further suggested that radicals are formed as intermediates from N-nitrosodialkylamines. The level of nitrosamine-induced lipid peroxidation parallels hepatocartgenicity in rats. These data, although preliminary, provide further evidence that free radical damage and DNA alkylation are involved in carcinogenesis induced by nitrosamines.