Abstract

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.

Highlights

  • Nanotoxicology is the study of nanomaterial toxicity

  • The approximate physical sizes (APS) measured in the report were similar to those in the data sheet provided by the manufacture

  • We hypothesized that cytotoxicity is a function of cell killing and suppression of cell proliferation and, as such, we assayed for cell viability, apoptosis, cellular proliferation, and cell cycle progression

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Summary

Introduction

Nanotoxicology is the study of nanomaterial toxicity. Nanomaterials are defined as any particulate or agglomerate that has at least one dimension in the size range from 1 to 100 nm [1]. Nanomaterials are being used with an increasing frequency in a variety of industries. Their use is common in semiconductors [2], electronics [3], pharmaceuticals [4], cosmetics [5], consumables [6], and drug delivery platforms being studied for cancer therapy [7]. With the use of nanomaterials increasing in frequency and application, exposure amongst the general public and occupational workers has become a concern. There have not been any epidemiological studies or clinical evidence of NPs causing adverse health effects in humans [12]. The National Institute for Occupational Safety and Health has designated workplace and occupation exposure limit recommendations for some particles based on their size. Certain regulations on consumer exposure through food have been established [6,14]

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