Differential Effects of Nano TiO₂ and CeO₂ on Normal Human Lung Epithelial Cells In Vitro

Abstract

<jats:p>Nano-TiO<jats:sub>2</jats:sub> and nano-CeO<jats:sub>2</jats:sub> are among the most widely used engineered nanoparticles (NPs). We investigated a variety of endpoints to assess the toxicity of eight of these NPs to induce potentially adverse health effects in an <jats:italic>In Vitro</jats:italic> human respiratory epithelial cell model. These endpoints include cytotoxicity, reactive oxygen species (ROS)/reactive nitrogen species (RNS) production, 8-hydroxy-2_-deoxyguanosine (8-oxo-dG), endogenous DNA adducts, Apurinic/apyrimidinic (AP) sites, 4-Hrdoxynonenal (4-HNE) protein adducts, Malondialdehyde (MDA) protein adducts, and genomics analysis on altered signaling pathways. Our results indicated that cytotoxicity assays are relatively insensitive, and we detected changes in other endpoints at concentrations much lower than those inducing cytotoxicity. Among the ROS-related endpoints, 8-oxo-dG is relatively more sensitive than other assays, and nano-TiO<jats:sub>2</jats:sub> induced more 8-oxo-dG formation than nano-CeO<jats:sub>2</jats:sub>. Finally, there are many signaling pathways changes at concentrations at which no cytotoxicity was observed. These alterations in signaling pathways correlated well with <jats:italic>In Vitro</jats:italic> toxicity that was observed at higher concentrations, and with in vivo adverse outcome pathways caused by nano-TiO<jats:sub>2</jats:sub> and nano-CeO<jats:sub>2</jats:sub> in experimental animals.</jats:p>

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