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人类胎儿肝脏中细胞色素P-450的分子毒理学

Molecular toxicology on cytochrome P-450 in human fetal livers.

作者信息

Kamataki T, Kitada M, Komori M

机构信息

Division of Analytical Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.

出版信息

J Toxicol Sci. 1991 Feb;16 Suppl 1:107-16. doi: 10.2131/jts.16.supplementi_107.

Abstract

Among mammalian species, humans and monkeys are sole species which possess cytochrome P-450 in the liver in fetal life. Cytochrome P-450 catalyzes oxidations of a wide variety of compounds including steroids, drugs and toxicants. Thus, the purpose of this study was to examine the toxicological significance of human fetal cytochrome P-450. Firstly, we found that human fetal livers were capable of activating numbers of carcinogenic compounds. Secondly, the capacity of human fetal cytochrome P-450 to activate mutagens and carcinogens was confirmed using purified forms of cytochrome P-450. For this, we purified four forms of cytochrome P-450 from human fetal livers. Lastly, we could isolate a cDNA clone coding for P-450HFLa which is one of the major forms of cytochrome P-450 in human fetal livers. Utilizing synthesized cD-NAs as probes, we found that this form of cytochrome was expressed specifically in fetuses.

摘要

在哺乳动物物种中,人类和猴子是仅有的在胎儿期肝脏中拥有细胞色素P-450的物种。细胞色素P-450催化多种化合物的氧化反应,包括类固醇、药物和毒物。因此,本研究的目的是探讨人类胎儿细胞色素P-450的毒理学意义。首先,我们发现人类胎儿肝脏能够激活多种致癌化合物。其次,使用纯化形式的细胞色素P-450证实了人类胎儿细胞色素P-450激活诱变剂和致癌物的能力。为此,我们从人类胎儿肝脏中纯化了四种细胞色素P-450形式。最后,我们能够分离出编码P-450HFLa的cDNA克隆,P-450HFLa是人类胎儿肝脏中细胞色素P-450的主要形式之一。利用合成的cDNA作为探针,我们发现这种细胞色素形式在胎儿中特异性表达。

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