Nickel-smelting fumes increased the expression of HIP-1α through PI3K/ERK pathway in NIH/3T3 cells

作者：Han, Dan; Yang, Yue; Zhang, Lin; Wang, Chao; Wang, Yue; Tan, Wen-Qiao; Hu, Xue-Ying; Wu, Yong-Hui^*

来源：Journal of Occupational Health, 2016, 58(5): 413-424.

DOI：10.1539/joh.15-0287-OA

• Animal toxicity
• Cytotoxicity
• HIF-1 alpha
• Kinase
• Nickel-smelting fumes

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-1 alpha, 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, p70S6K 1, and ERK proteins and increased HIF-1 alpha expression in a time-and dose-dependent manner. However, activation was suppressed when NIH/3T3 cells were pre-treated 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-1 alpha 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.

• 出版日期2016-9
• 单位哈尔滨医科大学