Metabolic activation of procarbazine. Evidence for carbon-centered free-radical intermediates.

The metabolism of procarbazine was studied using spin-trapping techniques. The oxidation of procarbazine, catalyzed by horseradish peroxidase, prostaglandin synthetase [ram seminal vesicle (RSV) microsomes] or rat hepatic microsomal cytochrome P-450, produced carbon-centered free radicals. Cytochrome P-450 also catalyzed this oxidation in the presence of hydrogen peroxide. Horseradish peroxidase activation of procarbazine formed both the methyl radical and the N-isopropylbenzylamide radical [(CH3)2CHNHCO(C6H4)CH2.]. In the presence of RSV or rat hepatic microsomes, mostly the benzyl-type radical was trapped, presumably due to the reactivity of the methyl radical.