title: Nickel-smelting fumes increased the expression of HIF-1α through PI3K/ERK pathway in NIH/3T3 cells.
abstract: OBJECTIVE
  The purpose of this study was to investigate the effects of Nickel (Ni) -smelting fumes on oncogenic proteins in vivo and in vitro.
  
  
  METHODS
  Ni fallout beside a Ni smelting furnace in a factory was sampled to study its toxic effect. The effects of Ni-smelting fumes on the regulation of PI3K and ERK signaling pathways and the important downstream hypoxia inducible factor, HIF-1α, were studied both in NIH/3T3 cells and in the lung tissue of rats. NIH/3T3 cell transformation induced by Ni-smelting fumes was also observed.
  
  
  RESULTS
  Ni-smelting fumes activated PI3K, p-AKT, p70S6K1, and ERK proteins and increased HIF-1α expression in a time- and dose-dependent manner. However, activation was suppressed when NIH/3T3 cells were pretreated with PI3K/AKT or ERK inhibitors. Ni-smelting fumes caused malignant transformation of NIH/3T3 cells.
  
  
  CONCLUSIONS
  Ni-smelting fumes increased the expression of HIF-1α through the PI3K/ERK pathway in NIH/3T3 cells and induced malignant transformation in these cells indicating that Ni-smelting fumes may be a potential carcinogen in mammalian cells.
authors.affiliation: Department of Occupational Health, Public Health College, Harbin Medical University.
authors.forename: Dan
authors.initials: D
authors.lastname: Han
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Wen-Qiao
authors.initials: WQ
authors.lastname: Tan
authors.forename: Xue-Ying
authors.initials: XY
authors.lastname: Hu
authors.forename: Yong-Hui
authors.initials: YH
authors.lastname: Wu
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002681:China; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects* / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008669:Metallurgy; D051379:Mice; D041681:NIH 3T3 Cells; D009532:Nickel / Q000009:adverse effects*; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000187:drug effects / Q000378:metabolism
chemical_list: D000393:Air Pollutants; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009532:Nickel; D019869:Phosphatidylinositol 3-Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D048049:Extracellular Signal-Regulated MAP Kinases