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Time-Course Determination of Cellular Stress Responses Elicited by Engineered Nanomaterials
Citation:
Prasad, R. Y., C. F. BLACKMAN, D. M. DEMARINI, AND S. SIMMONS. Time-Course Determination of Cellular Stress Responses Elicited by Engineered Nanomaterials. Presented at Society of Toxicology (SOT) Annnual Meeting, Washington, DC, March 06 - 10, 2011.
Impact/Purpose:
Here we examine time-sensitive biological response pathways affected by engineered nanomaterials using a battery of stable luciferase-reporter cell lines engineered using HepG2 cells.
Description:
Engineered nanomaterials are being incorporated continuously into consumer products, resulting in increased human exposures. The study 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 engineered using HepG2 cells. We measured the activity of three key stress responsive transcription factors: NFkB, Nrf2, and AP-1 after exposure to 6 titanium dioxide nanomaterials (nano-TiO2) with rutile, anatase, and rutile/anatase crystal structures, and2 cerium oxide nanomaterials (nano-CeO2) from various manufacturers. Exposure concentrations ranged from 1-100 ug/ml per nanomaterial at 6 and 24 h. Cytotoxicity was measured in parallel using the MTT assay. Dynamic light scattering was used to determine the size and zeta potential of the nanomaterials in medium. Our results show that there were significant changes in transcriptional activation at concentrations as low as 1 ug/ml. The 10 nm anatase nano-TiO2-elicited the highest effect, a ~2.5 fold increase in NFkB transcriptional activation at 100 ug/ml after 24 h. Nrf2 showed transcriptional activation by one nano-CeO2, showing ~1.5 fold activation at 100 ug/ml after 24h. AP1 activity increased ~1.3 fold in response to anatase/rutile nano-TiO2 at 1 ug/ml after 24h. Both anatase/rutile nano-TiO2 were cytotoxic at 100 ug/ml after 24 h. Our results demonstrate the potential for engineered nanomaterials to elicit cellular stress responses through the NFkB and Nrf2 pathways. [This is an abstract or proposed presentation and does not necessarily reflect EPA policy.]