Cytotoxicity of NiO and Ni(OH)2 Nanoparticles Is Mediated by Oxidative Stress-Induced Cell Death and Suppression of Cell Proliferation.

The use of nanomaterial-based products continues to grow with advancing technology. Understanding the potential toxicity of nanoparticles (NPs) is important to ensure that products containing them do not impose harmful effects to human or environmental health. In this study, we evaluated the comparative cytotoxicity between nickel oxide (NiO) and nickel hydroxide (Ni(OH)2) in human bronchoalveolar carcinoma (A549) and human hepatocellular carcinoma (HepG2) cell lines. Cellular viability studies revealed cell line-specific cytotoxicity in which nickel NPs were toxic to A549 cells but relatively nontoxic to HepG2 cells. Time-, concentration-, and particle-specific cytotoxicity was observed in A549 cells. NP-induced oxidative stress triggered dissipation of mitochondrial membrane potential and induction of caspase-3 enzyme activity. The subsequent apoptotic events led to reduction in cell number. In addition to cell death, suppression of cell proliferation played an essential role in regulating cell number. Collectively, the observed cell viability is a function of cell death and suppression of proliferation. Physical and chemical properties of NPs such as total surface area and metal dissolution are in agreement with the observed differential cytotoxicity. Understanding the properties of NPs is essential in informing the design of safer materials.

Differential Cytotoxicity Induced by Transition Metal Oxide Nanoparticles is a Function of Cell Killing and Suppression of Cell Proliferation.

The application of nanoparticles (NPs) in industry is on the rise, along with the potential for human exposure. While the toxicity of microscale equivalents has been studied, nanoscale materials exhibit different properties and bodily uptake, which limits the prediction ability of microscale models. Here, we examine the cytotoxicity of seven transition metal oxide NPs in the fourth period of the periodic table of the chemical elements. We hypothesized that NP-mediated cytotoxicity is a function of cell killing and suppression of cell proliferation. To test our hypothesis, transition metal oxide NPs were tested in a human lung cancer cell model (A549). Cells were exposed to a series of concentrations of TiO2, Cr2O3, Mn2O3, Fe2O3, NiO, CuO, or ZnO for either 24 or 48 h. All NPs aside from Cr2O3 and Fe2O3 showed a time- and dose-dependent decrease in viability. All NPs significantly inhibited cellular proliferation. The trend of cytotoxicity was in parallel with that of proliferative inhibition. Toxicity was ranked according to severity of cellular responses, revealing a strong correlation between viability, proliferation, and apoptosis. Cell cycle alteration was observed in the most toxic NPs, which may have contributed to promoting apoptosis and suppressing cell division rate. Collectively, our data support the hypothesis that cell killing and cell proliferative inhibition are essential independent variables in NP-mediated cytotoxicity.