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Oxidative Stress, Inflammation, and DNA Damage Responses Elicited by Silver, Titanium Dioxide, and Cerium Oxide Nanomaterials
Raju, P. Y., K. Wallace, C. F. BLACKMAN, D. M. DEMARINI, AND S. SIMMONS. Oxidative Stress, Inflammation, and DNA Damage Responses Elicited by Silver, Titanium Dioxide, and Cerium Oxide Nanomaterials. Presented at Genetics Enironmental Mutagenesis Society (GEMS) Fall Meeting, Chapel Hill, NC, November 08, 2011.
Here we examine time-sensitive biological response pathways affected by engineered nanomaterials using a battery of stable luciferase-reporter cell lines in HepG2 cells.
Previous literature on the biological effects of engineered nanomaterials has focused largely on oxidative stress and inflammation endpoints without further investigating potential pathways. Here we examine time-sensitive biological response pathways affected by engineered nanomaterials using a battery of stable luciferase-reporter cell lines in HepG2 cells. We measured the activation of five key stress responsive transcription factors, ELG-1, NFkB, Nrf2, AP-1 and the human promoter IL-8, by exposure to six titanium dioxide (nano-TiO2) with rutile, anatase, and rutile/anatase crystal structures, two cerium oxide (nano-CeO2-), and two citrate-capped silver (nano-Ag) nanomaterials. Exposure concentrations ranged from 1-100 ug/ml for nano-TiO2, and nano-CeO2, and 0.1-30 ug/ml for nano-Ag. Cells were exposed for 6, 16, and 24 h to each nanomaterial. Cytotoxicity was measured in parallel using the MTT assay for nano-Ti02 and nano-CeO2 and the Alamar Blue assay for nano-Ag. Dynamic light scattering was used to determine the size and zeta potential of the nanomaterials in medium. Nano-Ag 10 nm citrate elicited a ~12-fold increase in ELG-1 at 1 ug/ml after 24 h. When exposed to 100 ug/ml of 10 nm anatase nano-TiO2 for 24 h, NFkB transcriptional activation increased ~2.5 fold. Nrf2 transcriptional activation increased by one nano-CeO2, showing ~1.5 fold activation at 100 ug/ml after 24 h exposure. Anatase/rutile nano-TiO2 elicited a ~1.3 fold increase in AP1 at 1 ug/ml after 24 h exposure. Our results demonstrate the potential for engineered nanomaterials to elicit cellular stress responses, inflammation and DNA damage. [Abstract does not necessarily reflect the policies of the U.S. EPA.]
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
INTEGRATED SYSTEMS TOXICOLOGY DIVISION
GENETIC AND CELLULAR TOXICOLOGY BRANCH