Bp-7, 8-diol对表达大鼠肝细胞色素P450 中国仓鼠 V79 细胞毒性的研究

Bp-7, 8-diol对表达大鼠肝细胞色素P450 中国仓鼠 V79 细胞毒性的研究

崔景荣, N.P.E.Vermeulen

1. 中北京医科大学天然药物及仿生药物国家重点实验室, 北京 100083;
2. 荷兰自由大学化学系药物化学室分子毒理组山

收稿日期:1997-07-15 修回日期:1998-04-22 出版日期:1998-09-15 发布日期:1998-09-15

Cytotoxicity of Benzo(a)pyrene-7,8-dihydrodiol on Genetically Engineered V79 Chinese Hamster Cells Expressing Rat Liver Cytochrome P450 1A1

Jing-Rong Cui, N.P.E.Vermeulen

1. National Research Laboratory of Natural and Biomimetic Drugs; Beijing Medical University; Beijing 100083
2. Division of Molecular Toxicology; Department of Pharmacochemistry; Faculty of Chemistry; Free University, The Netherlands

Received:1997-07-15 Revised:1998-04-22 Online:1998-09-15 Published:1998-09-15

摘要/Abstract

摘要：

本文采用细胞计数和中性红摄取法观察了BP-7,8-diol 对XEM2 (稳定表达了大鼠肝细胞色素4501A1) 和V79 (未表达P450 1A1) 细胞生长的作用, 目的为建立体外细胞毒模型。结果表明, 在1.0、2.5、5.0 μmol·L^-1不同浓度下, BP-7,8-diol 对XEM2 细胞产生很强的毒性, 其毒性具有浓度和时间依赖性, 在相同的浓度下BP-7,8-diol 对V79 细胞并没有影响, 同时也发现, 细胞色素P450 酶抑制剂-αNF 对BP-7,8-diol 引起的细胞毒具有保护作用。这些结果说明, BP-7,8-diol 对XEM2 细胞毒性是通过细胞色素P450 1A1 的作用引起的。

关键词: V79细胞株, XEM2细胞株, P4501A1, BP-7,8-diol, 细胞毒性

Abstract: To develop well defined in vitro cell system to test cytotoxicity of a number of model toxins, genetically engineered V79 Chinese hamster fibroblasts expressing isoenzymes of cytochrome P4501A1 XEM2 cells and V79 cells (parental), which lack cytochrome P450 enzyme activities, were used as controls. The cytotoxic effect of trans 7,8 dihydrbenzo(a)pyrene (BP-7,8-diol) on the parental cells V79 and V79 derived XEM2 cells were evaluated by two methods for cell viability. The data obtained expressed that BP-7,8-diol ranging from 1.0 μmol·L^-1 to 5.0 μmol·L^-1 in concentrations incubated for 24 h showed a strong cytotoxic effect in XEM2 cells (expressing rat cytochrome P4501A1) in a concentration dependent manner. Time dependent decrease for survival of XEM2 cells was also observed at 2.5 μmol·L^-1 concentration. Likewise, BP-7,8-diol did not alter the survival of the parental cells V79 under the same condition. This study also showed that α naphthoflavone (αNF), a well known inhibitor of cytochrome P4501A1 might alter BP-7,8-diol induced cytotoxicity in the XEM2 cells. Our results suggested that cytochrome P4501A1 is responsible for BP-7,8-diol induced cytotoxicity.

Key words: V79 cell line, XEM2 cell line, BP-7,8-diol, Cytotoxicity P4501A1

Supporting:

崔景荣, N.P.E.Vermeulen. Bp-7, 8-diol对表达大鼠肝细胞色素P450 中国仓鼠 V79 细胞毒性的研究[J]. .

Jing-Rong Cui, N.P.E.Vermeulen . Cytotoxicity of Benzo(a)pyrene-7,8-dihydrodiol on Genetically Engineered V79 Chinese Hamster Cells Expressing Rat Liver Cytochrome P450 1A1 [J]. .

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