PRIMARY AROMATIC-AMINES - THEIR N-OXIDATIVE BIOACTIVATION

There exists a diversity of pathways in mammalian cells serving to act ivate primary aromatic amines. 1 N-Oxidative mixed-function turnover u sually involves participation of the cytochrome P450 superfamily, whil e catalysis by the flavin-containing monooxygenases is restricted to a few amines capable of forming imine tautomers. Surprisingly, haemoglo bin metabolizes cytotoxic and carcinogenic arylamines via a monooxygen ase-like mechanism, but peroxygenase activity is also operative. 2 In extrahepatic tissues that exhibit only a low level of monooxygenases, peroxidative transformations, as are brought about by prostaglandin H synthase, myeloperoxidase or lactoperoxidase, predominate in amine act ivation. Non-mammalian peroxidases frequently used as model systems in clude horseradish peroxidase and chloroperoxidase. 3 Non-enzymatic, li ght-induced conversion of aromatic amines to free radical or N-oxy pro ducts proceeds either via direct photolysis of the nitrogenous compoun ds or through attack by lipid-derived reactive intermediates generated during irradiation. 4 The interplay of the various tissue-specific pr ocesses of arylamine activation serves to explain differences in susce ptibility toward the biological actions of primary aromatic amines.