Sinha B K
Biochemical and Molecular Pharmacology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Free Radic Res Commun. 1991;15(4):189-95. doi: 10.3109/10715769109049140.
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.
利用自旋捕集技术,在完整的人早幼粒细胞白血病(HL60)和小鼠肝细胞系中研究了肼衍生物、丙卡巴肼和异烟肼代谢为活性自由基中间体的过程。虽然已证明HL60细胞同时含有髓过氧化物酶和细胞色素P - 450酶,但肝细胞系仅显示细胞色素P - 450活性。据报道,过氧化物酶和细胞色素P - 450均可催化肼的生物转化。丙卡巴肼和异烟肼在这些细胞系中分别迅速代谢为甲基和异丙基自由基。然而,在HL60细胞中,丙卡巴肼由髓过氧化物酶代谢,而异烟肼主要由细胞色素P - 450系统代谢。在肝细胞中,这两种化合物均由P - 450系统代谢。