Cytochrome P-450- and peroxidase-dependent activation of procarbazine and iproniazid in mammalian cells.
Metabolism of hydrazine derivatives, procarbazine and iproniazid, to reactive free radical intermediates has been studied using spin-trapping techniques in intact human promyelocytic leukemia (HL60) and mouse hepatic cell lines. While HL60 cells have been shown to contain both myeloperoxidase and cytochrome P-450 enzymes, the hepatic cell line shows only cytochrome P-450 activity. Both peroxidases and cytochrome P-450 have been reported to catalyze biotransformation of hydrazines. Procarbazine and iproniazid were rapidly metabolized in these cell lines to methyl and isopropyl radicals, respectively. However, in HL60 cells, procarbazine was metabolized by myeloperoxidase while iproniazid was metabolized mostly by the cytochrome P-450 system. In the hepatic cells, both of these compounds were metabolized by the P-450 system.
Sinha
B K
BK
Biochemical and Molecular Pharmacology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
D001711:Biotransformation; D002460:Cell Line; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006801:Humans; D007490:Iproniazid / Q000378:metabolism*; D015473:Leukemia, Promyelocytic, Acute; D008099:Liver / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism*; D011344:Procarbazine / Q000378:metabolism*
D005609:Free Radicals; D011344:Procarbazine; D003577:Cytochrome P-450 Enzyme System; D007490:Iproniazid; D009195:Peroxidase