Differential Effects of Nano TiO��� and CeO��� on Normal Human Lung Epithelial Cells .
Sheau-Fung Thai, Carlton P Jones, Garret B Nelson, Beena Vallanat, Micaela Killius, James L Crooks, William O Ward, Carl F Blackman, Jeffrey A Ross
Author Information
Sheau-Fung Thai: National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, 109 TW Alexander Dr., Durham, NC 27711, USA.
Carlton P Jones: National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, 109 TW Alexander Dr., Durham, NC 27711, USA.
Garret B Nelson: National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, 109 TW Alexander Dr., Durham, NC 27711, USA.
Beena Vallanat: National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, 109 TW Alexander Dr., Durham, NC 27711, USA.
Micaela Killius: National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, 109 TW Alexander Dr., Durham, NC 27711, USA.
James L Crooks: Division of Biostatistics and Bioinformatics, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.
William O Ward: National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, 109 TW Alexander Dr., Durham, NC 27711, USA.
Carl F Blackman: National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, 109 TW Alexander Dr., Durham, NC 27711, USA.
Jeffrey A Ross: National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, 109 TW Alexander Dr., Durham, NC 27711, USA.
Nano-TiO��� and nano-CeO��� 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 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��� induced more 8-oxo-dG formation than nano-CeO���. Finally, there are many signaling pathways changes at concentrations at which no cytotoxicity was observed. These alterations in signaling pathways correlated well with toxicity that was observed at higher concentrations, and with in vivo adverse outcome pathways caused by nano-TiO��� and nano-CeO��� in experimental animals.
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