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Differential effects of Nano TiO2 and CeO2 on normal human lung epithelial cells in vitro
Citation:
Thai, S., C. Jones, G. Nelson, B. Vallanat, M. Killius, J. Crooks, W. Ward, C. Blackman, AND J. Ross. Differential effects of Nano TiO2 and CeO2 on normal human lung epithelial cells in vitro. Journal of Nanoscience and Nanotechnology. American Scientific Publishers , VALENCIA, CA, 19(11):6907-6923, (2019). https://doi.org/10.1166/jnn.2019.16737
Impact/Purpose:
Engineered Nanomaterials (ENMs) are being widely used. Nano-TiO2 and nano-CeO2 are among the most used ENMs. However, the toxicity studies of these ENMs have not kept up with the usage. There are animal studies showing nano-TiO2 can cause rat lung tumor and. And worker exposed to nano-TiO2 dust resulted in pulmonary inflammation and fibrosis. Therefore, nano-TiO2 was classified as possible carcinogen to human by IARC. We treat normal human lung epithelial (BEAS-2B) cells with 6 nano-TiO2 and 2 nano-CeO2 particles. These ENMs are different in their sizes, chemical compositions, shape, surface area, and impurities. We examined different endpoints including cytotoxicity, ROS, ROS/RNS production, endogenous DNA adduct formation, AP sties, 8-oxo-dG, 4-HNE protein adducts, MDA protein adducts and signaling pathway alterations. Our results indicated that: 1. Cytotoxicity is a relatively insensitive assay. We can detect changes in other assays at the concentration well below any cytotoxicity were observed. 2. Endogenous DNA adduct formation and 8-oxo-dG formation are relative sensitive assays, and may be used for toxicity screen for ENMs. 3. Our results correlated with in vivo results where they also detected DNA damage in nano-TiO2 treated mice. 4. Among the altered signaling pathways, integrin signaling was altered in 6 out of 7 ENMs that gave enough differential expressed genes to upload to Ingenuity Pathway Analysis (IPA). Integrin may be one the first molecules that the ENMs came into contact on the cell surface. And many signaling pathways followed the direction (either induction or suppression) of the integrin signaling pathway indicating cross talk between these signaling pathways.
Description:
Nano-TiO2 and nano-CeO2 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 In Vitro 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-TiO2 induced more 8-oxo-dG formation than nano-CeO2. Finally, there are many signaling pathways changes at concentrations at which no cytotoxicity was observed. These alterations in signaling pathways correlated well with In Vitro toxicity that was observed at higher concentrations, and with in vivo adverse outcome pathways caused by nano-TiO2 and nano-CeO2 in experimental animals.
URLs/Downloads:
DOI: Differential effects of Nano TiO2 and CeO2 on normal human lung epithelial cells in vitro