Advance Access publication November 23, 2011 Zinc Oxide Nanoparticles Interfere With Zinc Ion Homeostasis to Cause

The toxicological effects of zinc oxide nanoparticles (ZnO-NPs) are attracting increasing concern as the field of nanotechnology progresses. Although the literature suggests that toxicity of ZnO-NPs may be related to their dissolution, the mechanism for ZnO-NP perturbation of cytosolic zinc concentration ([Zn21]c) homeostasis remains obscure. Using FluoZin-3 and RhodZin-3, this study investigated changes in both [Zn21]c and mitochondrial free Zn21 concentration ([Zn21]m) under conditions of ZnO-NP treatment in vivo and in vitro. In human leukemia Jurkat cells and human lung carcinoma H1355 cells, ZnO-NP treatment resulted in an elevation of both [Zn21]c and [Zn 21]m. In H1355 cells, ZnO-NP treatment induced depolarization of mitochondrial membrane potential, as well as caspase-3 activation and lactic dehydrogenase (LDH) release. In our in vivo experiments, when rats were expose