The size-dependent genotoxicity and oxidative stress of silica nanoparticles on endothelial cells.

Concerns over the health risk of the widely distributed, commonly used silica nanoparticles (SiNPs) are increasing worldwide. Yet, up to now, there are still many major knowledge gaps over the potential adverse effects of SiNP exposure on human cardiovascular health and the underlying mechanisms. In this study, comet assay and micronucleus test were employed to determine the genotoxic potentials of four sizes (10, 25, 50, 100 nm) of SiNPs to human umbilical vein endothelial cells (HUVECs) in culture. The intracellular redox statuses were explored through the determination of the levels of reactive oxygen species (ROS) and reduced glutathione (GSH) with kits, respectively. The protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) were also detected by Western blot. The results showed that at the administrative levels (1, 5, 25 μg/mL), all the four sizes of SiNPs could induce an increase of both DNA damages and MN frequencies in HUVECs in culture, with a positive dose- and negative size-dependent effect relationship (S100 < S50 < S25 < S10). Also, significantly enhanced levels of intracellular ROS, but decreased levels of GSH, were observed in the SiNP-treated groups. Interestingly, a very similar manner of dose- and size-dependent effect relationship was observed between the ROS test and both comet assay and MN test, but contrary to that of GSH assay. Correspondingly, the levels of Nrf2 protein were also enhanced in the SiNP-treated HUVECs, with a negative size-dependent effect relationship. These results implicated that induction of oxidative stress and subsequent genotoxicity may be an important biological mechanism by which SiNP exposure may affect human cardiovascular health.