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人胎盘中细胞色素P450酶的表达及环境调控

The expression and environmental regulation of P450 enzymes in human placenta.

作者信息

Pasanen M, Pelkonen O

机构信息

Department of Pharmacology and Toxicology, University of Kuopio, Finland.

出版信息

Crit Rev Toxicol. 1994;24(3):211-29. doi: 10.3109/10408449409021606.

DOI:10.3109/10408449409021606
PMID:7945891
Abstract

The human placenta oxidizes several xenobiotics, although the spectrum of substrates and metabolic activities when compared with the liver appears somewhat restricted. Maternal cigarette smoking or PCB exposure increases the expression of CYP1A1. This induced activity is able to catalyze the activation of benzo(a)pyrene (B(a)P) into DNA-bound products, both in vitro and in vivo. Studies on adult human liver bolster the concept that CYP1A1 and -1A2 are differentially expressed in hepatic and extrahepatic tissues. Studies with cDNA probe or enzyme specific antibodies and substrates for CYP2A, -2B, -2C, -2D, and -2E gene products have yielded negative results. There are only minimal activities that can be found in substantial quantities in placentas without maternal smoking; one example is 7-ethoxycoumarin O-deethylase (ECOD). Aromatase and cholesterol side-chain cleaving P450 mRNAs, proteins, and activities are measurable in human placentas and do not seem to be affected by maternal cigarette smoking.

摘要

人类胎盘可氧化多种外源性物质,不过与肝脏相比,其底物谱和代谢活性似乎有些受限。孕妇吸烟或接触多氯联苯会增加细胞色素P450 1A1(CYP1A1)的表达。这种诱导活性在体外和体内均能催化苯并(a)芘(B(a)P)活化为与DNA结合的产物。对成人肝脏的研究支持了CYP1A1和CYP1A2在肝组织和肝外组织中差异表达的观点。使用针对CYP2A、CYP2B、CYP2C、CYP2D和CYP2E基因产物的cDNA探针、酶特异性抗体及底物进行的研究均得出阴性结果。在未吸烟孕妇的胎盘中,只能检测到极少量的活性物质;例如7-乙氧基香豆素O-脱乙基酶(ECOD)。在人类胎盘中可检测到芳香化酶和胆固醇侧链裂解细胞色素P450的mRNA、蛋白质及活性,且似乎不受孕妇吸烟的影响。

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