Grantee Research Project Results
Final Report: Responses of Lung Cells to Metals in Manufactured Nanoparticles
EPA Grant Number: R831723Title: Responses of Lung Cells to Metals in Manufactured Nanoparticles
Investigators: Veranth, John , Reilly, Christopher A. , Yost, Garold S.
Institution: University of Utah
EPA Project Officer: Hahn, Intaek
Project Period: October 1, 2004 through September 30, 2007
Project Amount: $332,958
RFA: Exploratory Research to Anticipate Future Environmental Issues: Impacts of Manufactured Nanomaterials on Human Health and the Environment (2003) RFA Text | Recipients Lists
Research Category: Nanotechnology , Human Health , Safer Chemicals
Objective:
This research was based on the hypothesis that transition metals in particles induce pro-inflammatory signaling and cell damage through the production of reactive oxygen species. Established cell culture models and toxicology assays were applied to the analysis of manufactured nanoparticles containing metal and ceramic oxides. This work was motivated by the hypothesis that small physical size and high surface area of nanoparticles (d<30 nm) increases cellular uptake and induction of pro-inflammatory signaling compared to larger particles with the same elemental composition. The emphasis was on lower-cost nanomaterials that are sold in powder or liquid suspension form (TiO2, SiO2, Fe2O3, Al2O3, CeO) because these materials are expected to be produced and will ultimately be released in the largest amount. The initial focus was on lung epithelial cells but the work was extended to include vascular endothelial cells since vascular tissues are a major component of the lung and are exposed whenever particles translocate from the lung to systemic circulation.Summary/Accomplishments (Outputs/Outcomes):
Being able to detect and quantify nanoparticles in tissue is important for understanding the relative effects of solid metal oxide nanoparticles compared to soluble metal ions. We devoted efforts toward developing methods for quantifying solid nanoparticles in cultured cells and in lung tissue as a way to better understand the effect dose in particle toxicology experiments. We collaborated with researchers who have experience with particle detection by field flow-fractionation (FFF), and were able to demonstrate quantitative measurement of manufactured SiO2 particles in both lung cells and in rat lung tissue. These method development efforts involved adding known amounts of 70 nm particles to the biological sample followed by digestion and cleanup to remove the organic material that would interfere with the analysis. We were able to demonstrate detection of the 70 nm particles in rat lung tissue that contained a mixture of 70 and 250 nm particles. The results of this method demonstration were published in Particle and Fibre Toxicology, and a related publication appeared in Nano Letters.
The particle samples and particle characterization data from this study have been shared with another STAR grant (R833336, Dr. P. Moos, PI), which focuses on nanoparticles in the colon. This collaboration will result in publications that acknowledge EPA funding for both projects.
Journal Articles on this Report : 3 Displayed | Download in RIS Format
| Other project views: | All 7 publications | 4 publications in selected types | All 3 journal articles |
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Deering CE, Tadjiki S, Assemi S, Miller JD, Yost GS, Veranth JM. A novel method to detect unlabeled inorganic nanoparticles and submicron particles in tissue by sedimentation field-flow fractionation. Particle and Fibre Toxicology 2008;5:18. |
R831723 (Final) |
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Veranth JM, Kaser EG, Veranth MM, Koch M, Yost GS. Cytokine responses of human lung cells (BEAS-2B) treated with micron-sized and nanoparticles of metal oxides compared to soil dusts. Particle and Fibre Toxicology 2007;4:2. |
R831723 (Final) |
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Veranth JM, Cutler NS, Kaser EG, Reilly CA, Yost GS. Effects of cell type and culture media on Interleukin-6 secretion in response to environmental particles. Toxicology in Vitro 2008;22(2):498-509. |
R831723 (Final) |
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Supplemental Keywords:
air, bioavailability, dose-response, ultrafine particulate matter, in vitro, mammalian, cellular, metals, toxicology, Health, Scientific Discipline, Health Risk Assessment, Risk Assessments, Environmental Chemistry, cytokines, particle size, combustion emissions, human exposure, particulate matter, engineered nanomaterials, ambient particle health effects, nanotechnology, inhalation toxicology, human health risk, inhalation study, particle exposure, biochemical research, carbon fullereneProgress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.