Inhalation Toxicity of Particulate Matters Doped with Arsenic Induced Genotoxicity and Altered Akt Signaling Pathway in Lungs of Mice

Abstract

In the workplace, the arsenic is used in the semiconductor production and the manufacturing of pigments, glass, pesticides and fungicides. Therefore, workers may be exposed to airborne arsenic during its use in manufacturing. The purpose of this study was to evaluate the potential toxicity of particulate matters (PMs) doped with arsenic (PMs-Arsenic) using a rodent model and to compare the genotoxicity in various concentrations and to examine the role of PMs-Arsenic in the induction of signaling pathway in the lung. Mice were exposed to PMs 124.4 ± 24.5 μg/m3 (low concentration) , 220.2 ± 34.5 μg/m3 (middle concentration) , 426.4 ± 40.3 μg/m3 (high concentration) doped with arsenic 1.4 μg/m3 (Low concentration) ,2.5 μg/m3 (middle concentration) , 5.7 μg/m3 (high concentration) for 4 wks (6 h/d, 5 d/wk) , respectively in the whole-body inhalation exposure chambers. To determine the level of genotoxicity, Chromosomal aberration (CA) assay in splenic lymphocytes and Supravital micronucleus (SMN) assay were performed. Then, signal pathway in the lung was analyzed. In the genotoxicity experiments, the increases of aberrant cells were concentration-dependent. Also, PMs-arsenic caused peripheral blood micronucleus frequency at high concentration. The inhalation of PMs-Arsenic increased an expression of phosphorylated Akt (p-Akt: protein kinase B) and phpsphorylated mammalian target of rapamycin (p-mTOR) at high concentration group. Taken together, inhaled PMs-Arsenic caused genotoxicity and altered Akt signaling pathway in the lung. Therefore, the inhalation of PMs-Arsenic needs for a careful risk assessment in the workplace.