Characterization of increased drug metabolism activity in dimethyl sulfoxide (DMSO)-treated Huh7 hepatoma cells.
Characterization of increased drug metabolism activity in dimethyl sulfoxide (DMSO)-treated Huh7 hepatoma cells.
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DOI：
10.1080/00498250802613620
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发表时间：
2009-03
期刊：
影响因子：
--
通讯作者：
Jeong H
中科院分区：
文献类型：
--
作者：
Choi S;Sainz B Jr;Corcoran P;Uprichard S;Jeong H
1. 本研究的目的是表征 Huh7 细胞代谢药物的基线能力，并研究二甲亚砜 (DMSO) 处理后药物代谢是否得到增强。 2.通过定量实时聚合酶链式反应（RT-PCR）测定主要I期和II期酶的信使RNA（mRNA）水平，并通过分析相关代谢物产生率，使用探针药物检查主要药物代谢酶的活性。 3.对照Huh7细胞中药物代谢酶的表达水平通常非常低，但DMSO处理显着增加了大多数药物代谢酶以及其他肝脏特异性蛋白的mRNA水平。重要的是，功能测定证实药物代谢酶活性随之增加。此外，用 3-甲基胆蒽处理 Huh7 细胞可诱导细胞色素 P450 (CYP) 1A1 表达。 4. 结果表明，Huh7 细胞的 DMSO 处理显着增强了其分化状态，从而提高了这种常见细胞系作为体外肝细胞模型的实用性。
1. The objective of this study was to characterize Huh7 cells' baseline capacity to metabolize drugs and to investigate whether the drug metabolism was enhanced upon treatment with dimethyl sulfoxide (DMSO). 2. The messenger RNA (mRNA) levels of major Phase I and Phase II enzymes were determined by quantitative real-time-polymerase chain reaction (RT-PCR), and activities of major drug-metabolizing enzymes were examined using probe drugs by analysing relevant metabolite production rates. 3. The expression levels of drug-metabolizing enzymes in control Huh7 cells were generally very low, but DMSO treatment dramatically increased the mRNA levels of most drug-metabolizing enzymes as well as other liver-specific proteins. Importantly, functionality assays confirmed concomitant increases in drug-metabolizing enzyme activity. Additionally, treatment of the Huh7 cells with 3-methylcholanthrene induced cytochrome P450 (CYP) 1A1 expression. 4. The results indicate that DMSO treatment of Huh7 cells profoundly enhances their differentiation state, thus improving the usefulness of this common cell line as an in vitro hepatocyte model.
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