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Cellular Stress Response to Engineered Nanoparticles: Effect of Size, Surface Coating, and Cellular Uptake
Prasad, R., J. Mcgee, M. Killius, C. Blackman, D. DeMarini, AND Steve Simmons. Cellular Stress Response to Engineered Nanoparticles: Effect of Size, Surface Coating, and Cellular Uptake. Presented at Environmental Mutagen Society, September 07 - 14, 2012.
Presentation at the Environmental Mutagen Society Meeting, Bellevue, Washington, September 7-14, 2012
CELLULAR STRESS RESPONSE TO ENGINEERED NANOPARTICLES: EFFECT OF SIZE, SURFACE COATING, AND CELLULAR UPTAKE RY Prasad 1, JK McGee2, MG Killius1 D Ackerman2, CF Blackman2 DM DeMarini2 , SO Simmons2 1 Student Services Contractor, US EPA, RTP, NC 2 US EPA, RTP, NC The number of engineered nanoparticles in consumer products has grown exponentially in recent years, but toxicity assessment is insufficient. Metal and metal oxide nanoparticles have been shown to generate reactive oxygen species; however, studies have not investigated adequately the association between physicochemical characteristics of the nanoparticles and cellular stress response. Here we examine three key stress-responsive transcription factors (NFKB, NRF2, and AP- I) and the human IL-8 promoter pathways affected by Ti02, Ce02 and Ag nanoparticles using a battery of stable luciferase-reporter HepG2 cell lines. We further assess the oxidative stress response by measuring glutathione depletion and cytotoxicity. We found that smaller-sized Ag nanoparticles elicited greater transcriptional activation ofHepG2 cells than did larger-sized particles at concentrations as low as 1 11g/ml; Ti02 and Ce02 nanoparticles produced no increases in any ofthe reporter cell lines. Combined with glutathione depletion and cytotoxicity results, the nanoparticles ranked as follows in terms of induction of oxidative stress response: 10-nm citrate-coated Ag10-nm PVP-coa.ted Ag > 75-nm citrate coated Ag75-nm PVP-coated Ag > Ti0 2 > Ce02. In conclusion, we find that Ag nanoparticles are more potent than TiOz or Ce02 nanoparticles at inducing a cellular stress response and that the smallest Ag nanoparticle induces the greatest stress response. [Abstract or proposed presentation does not necessarily reflect the policies of the U.S. EPA.]