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人细胞色素P450IA2 cDNA在人淋巴母细胞系中的稳定表达:该酶在黄曲霉毒素B1代谢活化中的作用

Stable expression of human cytochrome P450IA2 cDNA in a human lymphoblastoid cell line: role of the enzyme in the metabolic activation of aflatoxin B1.

作者信息

Crespi C L, Steimel D T, Aoyama T, Gelboin H V, Gonzalez F J

机构信息

Gentest Corporation, Woburn, Massachusetts 01801.

出版信息

Mol Carcinog. 1990;3(1):5-8. doi: 10.1002/mc.2940030104.

DOI:10.1002/mc.2940030104
PMID:2108694
Abstract

A human lymphoblastoid cell line stably expressing a human cytochrome P450IA2 cDNA was developed. This recombinant cell line displayed P450IA2 protein and estradiol 2-hydroxylase activity, neither of which was detected in the parental cell line. The recombinant cell line was also approximately 1000-fold more sensitive to the cytotoxicity and mutagenicity of the carcinogenic mycotoxin aflatoxin B1 than was the parent cell line. The increase in mutagenicity was supported by a corresponding increase in the level of aflatoxin B1 binding to DNA in cells expressing P450IA2 relative to control cells.

摘要

构建了一种稳定表达人细胞色素P450IA2 cDNA的人淋巴母细胞系。该重组细胞系表现出P450IA2蛋白和雌二醇2-羟化酶活性,而在亲本细胞系中均未检测到。该重组细胞系对致癌霉菌毒素黄曲霉毒素B1的细胞毒性和致突变性的敏感性也比亲本细胞系高约1000倍。相对于对照细胞,在表达P450IA2的细胞中黄曲霉毒素B1与DNA结合水平的相应增加支持了致突变性的增加。

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引用本文的文献

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Protection against aflatoxin B1-induced cytotoxicity by expression of the cloned aflatoxin B1-aldehyde reductases rat AKR7A1 and human AKR7A3.通过克隆的黄曲霉毒素B1-醛还原酶大鼠AKR7A1和人AKR7A3的表达来抵御黄曲霉毒素B1诱导的细胞毒性。
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Genotoxicity of aflatoxin B1: evidence for a recombination-mediated mechanism in Saccharomyces cerevisiae.
黄曲霉毒素B1的遗传毒性:酿酒酵母中重组介导机制的证据。
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Development of Caco-2 cells expressing high levels of cDNA-derived cytochrome P4503A4.
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Introduction of cytochrome P450IA2 metabolic capability into cell lines genetically matched for DNA repair proficiency/deficiency.将细胞色素P450IA2代谢能力引入在DNA修复能力/缺陷方面基因匹配的细胞系。
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