Possible involvement of glutathione and p53 in trichloroethylene- and perchloroethylene-induced lipid peroxidation and apoptosis in human lung cancer cells

Shiang Jiuun Chen, Jia Lin Wang, Jian Hung Chen, Rong Nan Huang

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22 Scopus citations

Abstract

Trichloroethylene (TCE) and perchloroethylene (PERC) are volatile organic compounds (VOCs) that are primarily inhaled through the respiratory system. The aim of this study was to elucidate the role of glutathione (GSH) and p53 in TCE- and PERC-induced lung toxicity. Human lung adenocarcinoma cells NCI-H460 (p53-wild-type) have constitutively lower levels of GSH than NCI-H1299 (p53-null) cells. The results showed that exposure to vapor TCE and PERC produced a dose-dependent and more pronounced accumulation of H2O2 in p53-WT H460 than p53-null H1299 cells. The accumulation of H2O2 was accompanied by severe cellular damage, as indicated by the significant increase of lipid peroxidation and apoptosis in p53-WT H460 cells, but not p53-null H1299 cells. Cotreatment of p53-WT H460 cells with free radical scavengers, such as D-mannitol, uric acid, and sodium selenite, significantly attenuated the TCE- or PERC-induced lipid peroxidation. In contrast, depletion of GSH in p53-null H1299 cells enhanced TCE- or PERC-induced lipid peroxidation. The levels of p53 and Baxproteins were elevated, while Bcl-2 protein was downregulated in TCE- or PERC-treated p53-WT H460 cells. Activity of caspase 3, the apoptotic executioner, was also significantly enhanced in TCE- or PERC-treated cells. These data suggest that, in human lung cancer cells, GSH plays a vital role in the protection of TCE- and PERC-induced oxidative stress and apoptosis, which may be mediated through a p53-dependent pathway.

Original languageEnglish
Pages (from-to)464-472
Number of pages9
JournalFree Radical Biology and Medicine
Volume33
Issue number4
DOIs
StatePublished - 15 Aug 2002

Keywords

  • Apoptosis
  • Free radicals
  • Glutathione
  • Lipid peroxidation
  • p53
  • Perchloroethylene
  • Trichloroethylene

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