Induction of glutathione depletion, p53 protein accumulation and cellular transformation by tetrachlorohydroquinone, a toxic metabolite of pentachlorophenol

被引：45

作者：

Wang, YJ ^{[1
]}

Ho, YS ^{[1
]}

Chu, SW ^{[1
]}

Lien, HJ ^{[1
]}

Liu, TH ^{[1
]}

Lin, JK ^{[1
]}

机构：

[1] TAIPEI MED COLL,SCH MED TECHNOL,TAIPEI,TAIWAN

来源：

CHEMICO-BIOLOGICAL INTERACTIONS | 1997年 / 105卷 / 01期

关键词：

tetrachlorohydroquinone; glutathione depletion; p53; protein; transformation;

D O I：

10.1016/S0009-2797(97)00023-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

Glutathione (GSH) conjugate formation with tetrachlorohydroquione (TCHQ) and the GSH content in vivo were measured by capillary zone electrophoresis. A more than 60% depletion of GSH content was found in liver tissue of mice treated with TCHQ. In addition, p53 protein accumulation and DNA fragmentation was induced by TCHQ. A two-stage model of chemical transformation of mouse embryonic fibroblasts was used to elucidate the transformation activity of TCHQ in vitro, and a 33% foci formation efficiency was found at the concentration of 5 mu M. GSH depletion caused by TCHQ could abolish the protective ability of the cell against reactive oxygen species provided by GSH. When DNA was damaged, p53 protein accumulated in the nucleus and, in the case of severe damage, initiated apoptosis. TCHQ's ability to cause GSH depletion and DNA damage may play a role in the cytotoxic and genotoxic properties of its metabolic precursor, PCP. (C) 1997 Elsevier Science Ireland Ltd.

引用

页码：1 / 16

页数：16

共 43 条

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