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Differential genomic effects on canonical signaling pathways by two different CeO2 nanoparticles in HepG2 cells
Citation:
Kitchin, K., K. Wallace, C. Jones, H. Ren, B. Castellon, J. Crooks, AND S. Thai. Differential genomic effects on canonical signaling pathways by two different CeO2 nanoparticles in HepG2 cells. TOXICOLOGIST. Society of Toxicology, RESTON, VA, 138(1):216, (2014).
Impact/Purpose:
Nanoparticles composed of CeO2 are of particular interest in toxicological studies due to their growing use in pharmaceutics, biomedical products, cosmetics, polishing materials and as automotive fuel additives. Human liver HepG2 cells were exposed for three days to two different forms of nanoparticles both composed of CeO2 (0.3, 3 and 30 Ug/mL) and a genomic study performed. The two CeO2 nanoparticles have dry primary particle sizes of 8 nanometers {(M) made by NanoAmor} and 58 nanometers {(L) made by Alfa Aesar} and differ in various other physical-chemical properties as well. This systems biological genomic study showed that the major altered pathways were protein synthesis, stress response, proliferation/cell cycle, cytoskeleton remodeling/actin polymerization and cellular metabolism.
Description:
Differential genomic effects on signaling pathways by two different CeO2 nanoparticles in HepG2 cells. Sheau-Fung Thai1, Kathleen A. Wallace1, Carlton P. Jones1, Hongzu Ren2, Benjamin T. Castellon1, James Crooks2, Kirk T. Kitchin1. 1Integrated Systems Toxicology Divison, 2Research Cores Unit, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC, USA. Nanoparticles composed of CeO2 are of particular interest in toxicological studies due to their growing use in pharmaceutics, biomedical products, cosmetics, polishing materials and as automotive fuel additives. Human liver HepG2 cells were exposed for three days to two different forms of nanoparticles both composed of CeO2 (0.3, 3 and 30 Ug/mL) and a genomic study performed. The two CeO2 nanoparticles have dry primary particle sizes of 8 nanometers {(M) made by NanoAmor}and 58 nanometers {(L) made by Alfa Aesar}and differ in various other physical-chemical properties as well. This systems biological genomic study showed that the major altered pathways were protein synthesis, stress response, proliferation/cell cycle, cytoskeleton remodeling/actin polymerization and cellular metabolism. Some of the canonical pathways affected were mTOR signaling, EIF2 signaling, fatty acid activation, G2/M DNA damage checkpoint regulation, glycolysis and ubiquitination. Nanoparticle M showed a normal dose-response pattern with 363, 633 and 1273 differentially expressed genes (DEGs) at 0.3, 3 and 30 g/mL, respectively. M is more active than L in respect to altering the pathways of mitochondrial dysfunction, acute phase response, apoptosis, 14-3-3 mediated signaling, remodeling of epithelial adherens junction signaling, actin nucleation by ARP-WASP complex, and altered TCA cycle. However, L is more active than M in respect to the pathways of NRF2-mediated stress response and hepatic fibrosis/hepatic stellate cell activation. In summary, these two CeO2 nanoparticles effected both many shared and some differing toxicity pathways. Disclaimer: [This is an abstract or a proposed presentation and does not necessarily reflect EPA policy. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.]