| Autor: |
Boyadzhiev A; Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON K1A 0K9, Canada.; Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada., Wu D; Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON K1A 0K9, Canada., Avramescu ML; Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON K1A 0K9, Canada., Williams A; Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON K1A 0K9, Canada., Rasmussen P; Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON K1A 0K9, Canada.; Department of Earth and Environmental Sciences, University of Ottawa, Ottawa, ON K1N 6N5, Canada., Halappanavar S; Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON K1A 0K9, Canada.; Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada. |
| Abstrakt: |
The impact of solubility on the toxicity of metal oxide nanoparticles (MONPs) requires further exploration to ascertain the impact of the dissolved and particulate species on response. In this study, FE1 mouse lung epithelial cells were exposed for 2-48 h to 4 MONPs of varying solubility: zinc oxide, nickel oxide, aluminum oxide, and titanium dioxide, in addition to microparticle analogues and metal chloride equivalents. Previously published data from FE1 cells exposed for 2-48 h to copper oxide and copper chloride were examined in the context of exposures in the present study. Viability was assessed using Trypan Blue staining and transcriptomic responses via microarray analysis. Results indicate material solubility is not the sole property governing MONP toxicity. Transcriptional signaling through the 'HIF-1α Signaling' pathway describes the response to hypoxia, which also includes genes associated with processes such as oxidative stress and unfolded protein responses and represents a conserved response across all MONPs tested. The number of differentially expressed genes (DEGs) in this pathway correlated with apical toxicity, and a panel of the top ten ranked DEGs was constructed (Hmox1, Hspa1a, Hspa1b, Mmp10, Adm, Serpine1, Slc2a1, Egln1, Rasd1, Hk2), highlighting mechanistic differences among tested MONPs. The HIF-1α pathway is proposed as a biomarker of MONP exposure and toxicity that can help prioritize MONPs for further evaluation and guide specific testing strategies. |
