title: Possible involvement of glutathione and p53 in trichloroethylene- and perchloroethylene-induced lipid peroxidation and apoptosis in human lung cancer cells.
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 H(2)O(2) in p53-WT H460 than p53-null H1299 cells. The accumulation of H(2)O(2) 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 Bax proteins 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.
authors.affiliation: Department of Botany, National Taiwan University, Taipei, Taiwan, Republic of China.
authors.forename: Shiang-Jiuun
authors.initials: SJ
authors.lastname: Chen
authors.forename: Jia-Lin
authors.initials: JL
authors.lastname: Wang
authors.forename: Jian-Hung
authors.initials: JH
authors.lastname: Chen
authors.forename: Rong-Nan
authors.initials: RN
authors.lastname: Huang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D005740:Gases; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005978:Glutathione / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008353:Mannitol / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000502:physiology*; D018384:Oxidative Stress; D011518:Proto-Oncogene Proteins / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D018038:Sodium Selenite / Q000494:pharmacology; D013750:Tetrachloroethylene / Q000633:toxicity*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014241:Trichloroethylene / Q000633:toxicity*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D014527:Uric Acid / Q000494:pharmacology; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D016166:Free Radical Scavengers; D005740:Gases; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D014527:Uric Acid; D014241:Trichloroethylene; D008353:Mannitol; D006861:Hydrogen Peroxide; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D005978:Glutathione; D018038:Sodium Selenite; D013750:Tetrachloroethylene