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细胞色素P - 450和过氧化物酶依赖的丙卡巴肼和异烟肼在哺乳动物细胞中的激活作用。

Cytochrome P-450- and peroxidase-dependent activation of procarbazine and iproniazid in mammalian cells.

作者信息

Sinha B K

机构信息

Biochemical and Molecular Pharmacology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.

出版信息

Free Radic Res Commun. 1991;15(4):189-95. doi: 10.3109/10715769109049140.

DOI:10.3109/10715769109049140
PMID:1667771
Abstract

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.

摘要

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。

相似文献

1
Cytochrome P-450- and peroxidase-dependent activation of procarbazine and iproniazid in mammalian cells.细胞色素P - 450和过氧化物酶依赖的丙卡巴肼和异烟肼在哺乳动物细胞中的激活作用。
Free Radic Res Commun. 1991;15(4):189-95. doi: 10.3109/10715769109049140.
2
Spin trapping of free radical intermediates produced during the metabolism of isoniazid and iproniazid in isolated hepatocytes.在分离的肝细胞中异烟肼和异丙烟肼代谢过程中产生的自由基中间体的自旋捕获。
Biochem Pharmacol. 1987 Sep 15;36(18):2913-20. doi: 10.1016/0006-2952(87)90202-4.
3
Activation of hydrazine derivatives to free radicals in the perfused rat liver: a spin-trapping study.灌注大鼠肝脏中肼衍生物向自由基的激活:一项自旋捕获研究。
Biochim Biophys Acta. 1987 May 19;924(2):261-9. doi: 10.1016/0304-4165(87)90021-3.
4
Metabolic activation of procarbazine. Evidence for carbon-centered free-radical intermediates.丙卡巴肼的代谢活化。以碳为中心的自由基中间体的证据。
Biochem Pharmacol. 1984 Sep 1;33(17):2777-81. doi: 10.1016/0006-2952(84)90695-6.
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Enzymatic activation of hydrazine derivatives. A spin-trapping study.肼衍生物的酶促活化。自旋捕获研究。
J Biol Chem. 1983 Jan 25;258(2):796-801.
6
In vitro and in vivo evidence for the formation of methyl radical from procarbazine: a spin-trapping study.来自丙卡巴肼的甲基自由基形成的体外和体内证据:一项自旋捕获研究。
Carcinogenesis. 1992 May;13(5):799-805. doi: 10.1093/carcin/13.5.799.
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Oxidative metabolism of some hydrazine derivatives by rat liver and lung tissue fractions.
J Biochem Toxicol. 1986 Mar;1(1):41-52. doi: 10.1002/jbt.2570010106.
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Free radical-mediated activation of hydrazine derivatives.自由基介导的肼衍生物活化。
Environ Health Perspect. 1985 Dec;64:179-84. doi: 10.1289/ehp.8564179.
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Detection of free radical intermediates in the oxidative metabolism of carcinogenic hydrazine derivatives.致癌肼衍生物氧化代谢过程中自由基中间体的检测
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Possible role of free radical intermediates in hepatotoxicity of hydrazine derivatives.
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Br J Cancer Suppl. 1996 Jul;27:S172-6.
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Oxidative denitrification of N omega-hydroxy-L-arginine by the superoxide radical anion.超氧阴离子自由基对Nω-羟基-L-精氨酸的氧化脱氮作用。
Biochem J. 1996 Jul 1;317 ( Pt 1)(Pt 1):17-21. doi: 10.1042/bj3170017.