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.
D000818:Animals; D001711:Biotransformation; D003497:Cyclic N-Oxides / Q000494:pharmacology; D005609:Free Radicals; D006735:Horseradish Peroxidase / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D011344:Procarbazine / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000494:pharmacology; D051381:Rats; D012669:Seminal Vesicles / Q000378:metabolism; D012756:Sheep; D013113:Spin Labels
D003497:Cyclic N-Oxides; D005609:Free Radicals; D013113:Spin Labels; D011344:Procarbazine; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D006735:Horseradish Peroxidase; D011451:Prostaglandin-Endoperoxide Synthases