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原代培养大鼠胎肝细胞中药物代谢酶的表达与诱导

Expression and induction of drug-metabolizing enzymes in cultured fetal rat hepatocytes.

作者信息

Kremers P, Roelandt L, Stouvenakers N, Goffinet G, Thome J P

机构信息

Universite de Liège, Laboratoire de Chimie Médicale, Sart Tilman, Belgium.

出版信息

Cell Biol Toxicol. 1994 Apr;10(2):117-25. doi: 10.1007/BF00756492.

DOI:10.1007/BF00756492
PMID:7953909
Abstract

An in vitro experimental model, fetal rat hepatocytes in culture, was metabolically characterized. Several enzymatic activities were expressed in these hepatocytes, namely, testosterone hydroxylations. Hepatocytes cultured up to 3 weeks in the presence of dexamethasone and phenobarbital still expressed some drug-metabolizing enzyme activities (e.g., ECOD). The enzymatic activities were measured both directly on monolayers during culture and on the corresponding harvested and homogenized cells. The results correlate perfectly with each other. The 'on cell' procedure allows us to repeat the assay or to measure several activities on the same cells at different time intervals. The presence of dexamethasone in the culture medium allows the expression and the induction of several cytochrome P450 isoenzymes, namely, those hydroxylating testosterone. This makes the model particularly attractive for induction experiments as well as for metabolic or toxicological studies needing longer treatments.

摘要

一种体外实验模型,即培养的胎鼠肝细胞,进行了代谢特性分析。这些肝细胞表达了几种酶活性,即睾酮羟化酶活性。在存在地塞米松和苯巴比妥的情况下培养长达3周的肝细胞仍表达一些药物代谢酶活性(例如,乙氧黄酮脱乙基酶)。酶活性在培养期间直接在单层细胞上以及在相应收获并匀浆的细胞上进行测量。结果彼此完美相关。“细胞上”操作使我们能够重复测定或在不同时间间隔对同一细胞测量几种活性。培养基中地塞米松的存在允许几种细胞色素P450同工酶的表达和诱导,即那些使睾酮羟化的同工酶。这使得该模型对于诱导实验以及需要更长时间处理的代谢或毒理学研究特别有吸引力。

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本文引用的文献

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Regulation of gene expression in adult rat hepatocytes cultured on a basement membrane matrix.在基底膜基质上培养的成年大鼠肝细胞中基因表达的调控
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Interactions of hepatic cytochromes P-450 with steroid hormones. Regioselectivity and stereospecificity of steroid metabolism and hormonal regulation of rat P-450 enzyme expression.肝细胞色素P-450与甾体激素的相互作用。甾体代谢的区域选择性和立体特异性以及大鼠P-450酶表达的激素调节。
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