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

Ying Jan Wang; Yuan Soon Ho; Shen Way Chu; Heng Jung Lien; Ting Hsiu Liu; Jen Kun Lin

doi:10.1016/S0009-2797(97)00023-9

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

Ying Jan Wang, Yuan Soon Ho, Shen Way Chu, Heng Jung Lien, Ting Hsiu Liu, Jen Kun Lin

Research output: Contribution to journal › Article › peer-review

41 Citations (Scopus)

Abstract

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 μM. 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.

Original language	English
Pages (from-to)	1-16
Number of pages	16
Journal	Chemico-Biological Interactions
Volume	105
Issue number	1
DOIs	https://doi.org/10.1016/S0009-2797(97)00023-9
Publication status	Published - Jun 6 1997

Keywords

Glutathione depletion
Tetrachlorohydroquinone
Transformation
p53 protein

ASJC Scopus subject areas

Toxicology

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10.1016/S0009-2797(97)00023-9

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

abstract = "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 μM. 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.",

keywords = "Glutathione depletion, Tetrachlorohydroquinone, Transformation, p53 protein",

author = "Wang, {Ying Jan} and Ho, {Yuan Soon} and Chu, {Shen Way} and Lien, {Heng Jung} and Liu, {Ting Hsiu} and Lin, {Jen Kun}",

note = "Funding Information: This study was supported by the National Science Council grant NSC 86-2314-B-002-042 and by the National Health Research Institute grant DOH 86-HR-403. ",

year = "1997",

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doi = "10.1016/S0009-2797(97)00023-9",

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AU - Wang, Ying Jan

AU - Ho, Yuan Soon

AU - Chu, Shen Way

AU - Lien, Heng Jung

AU - Liu, Ting Hsiu

AU - Lin, Jen Kun

N1 - Funding Information: This study was supported by the National Science Council grant NSC 86-2314-B-002-042 and by the National Health Research Institute grant DOH 86-HR-403.

PY - 1997/6/6

Y1 - 1997/6/6

N2 - 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 μM. 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.

AB - 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 μM. 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.

KW - Glutathione depletion

KW - Tetrachlorohydroquinone

KW - Transformation

KW - p53 protein

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

Abstract

Keywords

ASJC Scopus subject areas

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