On the significance of the cytochrome P-450-dependent hydroxyl radical-mediated oxygenation mechanism

Abstract

1. Reconstituted membrane vesicles containing purified preparations of cytochrome P-450 LM2 and NADPH-cytochrome P-450 reductase effectively destroyed 2-deoxy-D-ribose in an NADPH-dependent process. 2. The destruction was mediated by hydroxyl radicals formed in an iron-catalysed Haber-Weiss reaction between superoxide anions and hydrogen peroxide liberated from the haemoprotein. 3. Administration of ethanol or benzene to rabbits, compounds known to be oxygenated by the hydroxyl radical-dependent mechanism, resulted in induction of a species of cytochrome P-450 effective in the radical-dependent metabolism of both chemicals. 4. Benzene treatment of rabbits also resulted in an enhanced hydroxyl radicaldependent metabolism of ethanol and benzene in liver microsomes. 5. It is suggested that, for certain substrates, hydroxyl radical-mediated cytochrome P-450-dependent oxygenation reactions are of importance for the microsomal metabolism of these compounds. 6. It is speculated that radical-producing species of cytochrome P-450 may contribute to hydroxyl radical-mediated cell damage.