Investigation on Mechanism of Growth Arrest Induced by Iron Oxide Nanoparticles in PC12 Cells

Iron oxide nanoparticles (Fe₃O₄ NPs) have recently received increasing interest in the biotechnology and life science. However, little is known about the nanoneurotoxicity of Fe₃O₄ NPs following exposure to neurons. This study was to elucidate the cytotoxicity and DNA damage of Fe₃O₄ NPs on PC12 cells line which derived from Rattus norvegicus pheochromocytoma. The cell viability was observed by MTS assay and cell cycle status was analyzed using flow cytometry. DNA damage related gene (P53) and its downstream targets (P21 and GADD45) were determined by semiquantitative RT-PCR. The results showed that exposure to Fe₃O₄ NPs at dosage levels between 25 and 200 μg/ml decreased cell viability respectively. The nanoparticles treatment caused cell cycle arrest in G2/M phase and the mRNA levels of P53 increased when PC12 cells were incubated with different concentrations Fe₃O₄ NPs. However, P21 and GADD45, the downstream targets of P53, were not affected. In summary, exposure to Fe₃O₄ NPs resulted in a dose-dependent cytotoxicity in cultured PC12 cells that was associated with increased P53 gene expression and much attention should be paid to the potential impact of Fe₃O₄ NPs on the central nervous system.