Primary aromatic amines: their N-oxidative bioactivation.
There exists a diversity of pathways in mammalian cells serving to activate primary aromatic amines. 1 N-Oxidative mixed-function turnover usually involves participation of the cytochrome P450 superfamily, while catalysis by the flavin-containing monooxygenases is restricted to a few amines capable of forming imine tautomers. Surprisingly, haemoglobin metabolizes cytotoxic and carcinogenic arylamines via a monooxygenase-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 activation. Non-mammalian peroxidases frequently used as model systems include horseradish peroxidase and chloroperoxidase. 3 Non-enzymatic, light-induced conversion of aromatic amines to free radical or N-oxy products proceeds either via direct photolysis of the nitrogenous compounds or through attack by lipid-derived reactive intermediates generated during irradiation. 4 The interplay of the various tissue-specific processes of arylamine activation serves to explain differences in susceptibility toward the biological actions of primary aromatic amines.
Hlavica
P
P
Walther-Straub-Institut für Pharmokologie und Toxikologie, Universität München, Germany.
Golly
I
I
Lehnerer
M
M
Schulze
J
J
D000588:Amines / Q000493:pharmacokinetics*; D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D006838:Hydrocarbons / Q000493:pharmacokinetics; D010100:Oxygen; D009195:Peroxidase / Q000378:metabolism; D013045:Species Specificity
D000588:Amines; D006838:Hydrocarbons; D003577:Cytochrome P-450 Enzyme System; D009195:Peroxidase; D010100:Oxygen