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 journalArticle

37 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 languageEnglish
Pages (from-to)1-16
Number of pages16
JournalChemico-Biological Interactions
Volume105
Issue number1
DOIs
Publication statusPublished - Jun 6 1997

Keywords

  • Glutathione depletion
  • p53 protein
  • Tetrachlorohydroquinone
  • Transformation

ASJC Scopus subject areas

  • Toxicology

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