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

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, p70S6K 1, and ERK proteins and increased HIF‐1α expression in a time‐and dose‐dependent manner. However, activation was suppressed when NIH / 3 T 3 cells were pretreated with PI 3 K / 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.