Toxicity of nano- and micro-sized ZnO particles in human lung epithelial cells
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This is the first comprehensive study to evaluate the cytotoxicity, biochemical mechanisms of toxicity, and oxidative DNA damage caused by exposing human bronchoalveolar carcinoma-derived cells (A549) to 70 and 420 nm ZnO particles. Particles of either size significantly reduced cell viability in a dose- and time-dependent manner within a rather narrow dosage range. Particle mass-based dosimetry and particle-specific surface area-based dosimetry yielded two distinct patterns of cytotoxicity in both 70 and 420 nm ZnO particles. Elevated levels of reactive oxygen species (ROS) resulted in intracellular oxidative stress, lipid peroxidation, cell membrane leakage, and oxidative DNA damage. The protective effect of N-acetylcysteine on ZnO-induced cytotoxicity further implicated oxidative stress in the cytotoxicity. Free Zn2+ and metal impurities were not major contributors of ROS induction as indicated by limited free Zn2+ cytotoxicity, extent of Zn2+ dissociation in the cell culture medium, and inductively-coupled plasma-mass spectrometry metal analysis. We conclude that (1) exposure to both sizes of ZnO particles leads to dose- and time-dependent cytotoxicity reflected in oxidative stress, lipid peroxidation, cell membrane damage, and oxidative DNA damage, (2) ZnO particles exhibit a much steeper dose–response pattern unseen in other metal oxides, and (3) neither free Zn2+ nor metal impurity in the ZnO particle samples is the cause of cytotoxicity.
KeywordsZnO Particles Oxidative stress Lipid peroxidation Oxidative DNA damage Human bronchoalveolar carcinoma-derived cell (A549) Nanotechnology Occupational health EHS
The authors thank the financial support from the Departments of Biological Sciences and Chemistry, Environmental Research Center, and the M S&T cDNA Resource Center at the Missouri University of Science and Technology. The authors thank Honglan Shi for ICP-MS analysis. Robert S. Aronstam contributed to technical editing of this manuscript.
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