Authors: Weisheng Lin Yi Xu ChuanChin Huang Yinfa Ma Katie B Shannon DaRen Chen YueWern Huang
Publish Date: 2008/06/10
Volume: 11, Issue: 1, Pages: 25-39
Abstract
This is the first comprehensive study to evaluate the cytotoxicity biochemical mechanisms of toxicity and oxidative DNA damage caused by exposing human bronchoalveolar carcinomaderived cells A549 to 70 and 420 nm ZnO particles Particles of either size significantly reduced cell viability in a dose and timedependent manner within a rather narrow dosage range Particle massbased dosimetry and particlespecific surface areabased 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 Nacetylcysteine on ZnOinduced 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 inductivelycoupled plasmamass spectrometry metal analysis We conclude that 1 exposure to both sizes of ZnO particles leads to dose and timedependent 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 cytotoxicityThe authors thank the financial support from the Departments of Biological Sciences and Chemistry Environmental Research Center and the M ST cDNA Resource Center at the Missouri University of Science and Technology The authors thank Honglan Shi for ICPMS analysis Robert S Aronstam contributed to technical editing of this manuscript
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