2011 Progress Report: Ultrafine Particle Cell Interactions In Vitro: Molecular Mechanisms Leading To Altered Gene Expression in Relation to Particle Composition

EPA Grant Number: R832415C005
Subproject: this is subproject number 005 , established and managed by the Center Director under grant R832415
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Rochester PM Center
Center Director: Oberdörster, Günter
Title: Ultrafine Particle Cell Interactions In Vitro: Molecular Mechanisms Leading To Altered Gene Expression in Relation to Particle Composition
Investigators: Finkelstein, Jacob N. , Oakes, David , Phipps, Richard , Prather, Kimberly A. , Rahman, Arshad
Institution: University of Rochester , University of California - San Diego
EPA Project Officer: Chung, Serena
Project Period: October 1, 2005 through September 30, 2010 (Extended to September 30, 2012)
Project Period Covered by this Report: October 1, 2010 through September 30,2011
RFA: Particulate Matter Research Centers (2004) RFA Text |  Recipients Lists
Research Category: Health Effects , Air

Objective:

The experiments proposed within this project are designed to address specific mechanistic hypotheses regarding the interactions between inhaled ultrafine particles and specific pulmonary cell populations. In vitro experiments are best utilized to provide a mechanistic link and biological plausibility for the whole animal and controlled clinical (human) exposures, described in the other programs of this Particle Center. In some circumstances they can be used to screen materials for acute toxicity or provide an initial ranking of response. In our original proposal we had suggested a focus on identifying specific responses and mechanisms that may be involved in the enhanced susceptibility of diabetic. We continue to explore this in the context of the oxidant stress hypothesis of PM induced effects.

Progress Summary:

During the past year we have focused on developing approaches that could be used to measure cellular responses to collected and fractionated sample of ambient ultrafine PM. Our strategy has been to use samples obtained by Kim Prather from various sources using a novel growth tube device that would increase the yield of material available for testing. Each sample was adjusted to the same final concentration and evaluated in our indicator A549 cell line. Our previous work has shown these cells to be useful as a screen for the ability of particle samples to induce oxidative stress. The characteristics of the samples collected between the Ports of Long Beach and Los Angeles are shown in Table 1 and the cellular data in Figure 1. Parallel to the collection of these samples, physical and chemical ambient measurements of atmospheric gas and aerosols were made. From these measurements, it was determined that the major sources of the particles were marine diesel combustion, local diesel pollution, nearby freeway pollution, biomass burning, and transport of pollution from California’s Central Valley.
 
 
 
The first four samples (B1-B4) taken with the growth tube impinger correspond with increased amounts of detected marine diesel particles. Thus, the results indicate that the aerosol containing ultrafine PM from marine diesel engines are significantly more reactive inducing oxidative stress than ultrafine TiO2 particles. Further analyses establishing dose-response curve need to be performed.
 


Journal Articles on this Report : 10 Displayed | Download in RIS Format

Other subproject views: All 13 publications 11 publications in selected types All 10 journal articles
Other center views: All 190 publications 156 publications in selected types All 143 journal articles
Type Citation Sub Project Document Sources
Journal Article Elder ACP, Gelein R, Azadniv M, Frampton M, Finkelstein J, Oberdorster G. Systemic effects of inhaled ultrafine particles in two compromised, aged rat strains. Inhalation Toxicology 2004;16(6-7):461-471. R832415 (2010)
R832415 (2011)
R832415 (Final)
R832415C003 (2011)
R832415C004 (2011)
R832415C005 (2011)
R826784 (Final)
R827354 (Final)
R827354C003 (Final)
R827354C004 (2003)
R827354C004 (Final)
R827354C005 (Final)
R828046 (Final)
  • Abstract from PubMed
  • Abstract: Taylor&Francis-Abstract
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  • Journal Article Elder ACP, Gelein R, Oberdorster G, Finkelstein J, Notter R, Wang Z. Efficient depletion of alveolar macrophages using intratracheally inhaled aerosols of liposome-encapsulated clodronate. Experimental Lung Research 2004;30(2):105-120. R832415 (2010)
    R832415 (2011)
    R832415 (Final)
    R832415C004 (2011)
    R832415C005 (2011)
    R827354 (Final)
    R827354C003 (Final)
    R827354C004 (2003)
    R827354C004 (Final)
    R827354C005 (Final)
  • Abstract from PubMed
  • Abstract: Taylor and Francis-Abstract
    Exit
  • Journal Article Elder A, Gelein R, Finkelstein J, Phipps R, Frampton M, Utell M, Kittelson DB, Watts WF, Hopke P, Jeong C-H, Kim E, Liu W, Zhao W, Zhuo L, Vincent R, Kumarathasan P, Oberdorster G. On-road exposure to highway aerosols. 2. Exposures of aged, compromised rats. Inhalation Toxicology 2004;16(Suppl 1):41-53. R832415 (2010)
    R832415 (2011)
    R832415 (Final)
    R832415C003 (2011)
    R832415C004 (2011)
    R832415C005 (2011)
    R827354 (Final)
    R827354C003 (Final)
    R827354C004 (2003)
    R827354C004 (Final)
    R827354C005 (Final)
    R828046 (Final)
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  • Abstract: Taylor and Francis-Abstract
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  • Journal Article Elder A, Johnston C, Gelein R, Finkelstein J, Wang Z, Notter R, Oberdorster G. Lung inflammation induced by endotoxin is enhanced in rats depleted of alveolar macrophages with aerosolized clodronate. Experimental Lung Research 2005;31(6):527-546. R832415 (2010)
    R832415 (2011)
    R832415 (Final)
    R832415C004 (2011)
    R832415C005 (2011)
    R827354 (Final)
    R827354C004 (Final)
    R827354C005 (Final)
    R828046 (Final)
  • Abstract from PubMed
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  • Journal Article Elder A, Gelein R, Silva V, Feikert T, Opanashuk L, Carter J, Potter R, Maynard A, Ito Y, Finkelstein J, Oberdorster G. Translocation of inhaled ultrafine manganese oxide particles to the central nervous system. Environmental Health Perspectives 2006;114(8):1172-1178. R832415 (2010)
    R832415 (2011)
    R832415 (Final)
    R832415C004 (2011)
    R832415C005 (2011)
    R827354 (Final)
    R827354C004 (Final)
    R827354C005 (Final)
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  • Abstract from PubMed
  • Associated PubMed link
  • Journal Article Fanning EW, Froines JR, Utell MJ, Lippmann M, Oberdorster G, Frampton M, Godleski J, Larson TV. Particulate Matter (PM) Research Centers (1999-2005) and the role of interdisciplinary center-based research. Environmental Health Perspectives 2009;117(2):167-174. R832415 (2010)
    R832415 (2011)
    R832415 (Final)
    R832415C003 (2011)
    R832415C004 (2011)
    R832415C005 (2011)
    R827351 (Final)
    R827352 (Final)
    R827353 (Final)
    R827354 (Final)
    R827355 (Final)
    R832416 (2009)
    R832416C003 (2009)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: EHP-Full Text PDF
  • Abstract: EHP-Abstract and Full Text HTML
  • Journal Article Han X, Gelein R, Corson N, Wade-Mercer P, Jiang J, Biswas P, Finkelstein JN, Elder A, Oberdorster G. Validation of an LDH assay for assessing nanoparticle toxicity. Toxicology 2011;287(1-3):99-104. R832415 (2011)
    R832415 (Final)
    R832415C004 (2011)
    R832415C005 (2011)
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  • Full-text: ScienceDirect-Full Text HTML
    Exit
  • Abstract: ScienceDirect-Abstract
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  • Other: ScienceDirect-Full Text PDF
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  • Journal Article Rushton EK, Jiang J, Leonard SS, Eberly S, Castranova V, Biswas P, Elder A, Han X, Gelein R, Finkelstein J, Oberdorster G. Concept of assessing nanoparticle hazards considering nanoparticle dosemetric and chemical/biological response metrics. Journal of Toxicology and Environmental Health, Part A 2010;73(5-6):445-461. R832415 (2010)
    R832415 (2011)
    R832415 (Final)
    R832415C004 (2010)
    R832415C004 (2011)
    R832415C005 (2010)
    R832415C005 (2011)
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  • Abstract: Taylor & Francis-Abstract
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  • Journal Article Singal M, Finkelstein JN. Use of indicator cell lines for determining inflammatory gene changes and screening the inflammatory potential of particulate and non-particulate stimuli. Inhalation Toxicology 2005;17(9):415-425. R832415 (2010)
    R832415 (Final)
    R832415C005 (2011)
    R827354 (Final)
    R827354C005 (Final)
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  • Abstract: Taylor and Francis-Abstract
    Exit
  • Journal Article Singal M, Finkelstein JN. Amorphous silica particles promote inflammatory gene expression through the redox sensitive transcription factor, AP-1, in alveolar epithelial cells. Experimental Lung Research 2005;31(6):581-597. R832415 (2010)
    R832415 (Final)
    R832415C005 (2011)
    R827354 (Final)
    R827354C005 (Final)
  • Abstract from PubMed
  • Abstract: Taylor and Francis-Abstract
    Exit
  • Supplemental Keywords:

    RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Air, particulate matter, Genetics, Health Risk Assessment, Risk Assessments, Physical Processes, Biology, altered gene expression, atmospheric particulate matter, atmospheric particles, long term exposure, airway disease, exposure, human exposure, ambient particle health effects, atmospheric aerosol particles, PM, aersol particles

    Progress and Final Reports:

    Original Abstract
  • 2006 Progress Report
  • 2007 Progress Report
  • 2008 Progress Report
  • 2009 Progress Report
  • 2010 Progress Report
  • Final Report

  • Main Center Abstract and Reports:

    R832415    Rochester PM Center

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R832415C001 Characterization and Source Apportionment
    R832415C002 Epidemiological Studies on Extra Pulmonary Effects of Fresh and Aged Urban Aerosols from Different Sources
    R832415C003 Human Clinical Studies of Concentrated Ambient Ultrafine and Fine Particles
    R832415C004 Animal models: Cardiovascular Disease, CNS Injury and Ultrafine Particle Biokinetics
    R832415C005 Ultrafine Particle Cell Interactions In Vitro: Molecular Mechanisms Leading To Altered Gene Expression in Relation to Particle Composition