Grantee Research Project Results

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. , Prather, Kimberly A. , Phipps, Richard , Oakes, David , Rahman, Arshad
Current Investigators: Finkelstein, Jacob N. , Prather, Kimberly A. , Rahman, Arshad , Oakes, David , Phipps, Richard
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: Human Health , 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 Californias Central Valley.

Table 1. Collection of Samples from the Ports of Long Beach and Los Angeles, California.

Sample #	Start	Stop	Volume syringe (mL)	total minutes	Estimated Concentraion (ug/mL)
B01	05/10/11 19:23	05/11/11 06:10	14.0	647	13.1
B02	05/11/11 06:20	05/11/11 12:15	13.0	647	9.5
B03	05/11/11 12:21	05/11/11 17:42	11.0	321	10.4
B04	05/11/11 17:51	05/12/11 06:05	15.0	734	12.8
B05	05/12/11 06:14	05/12/11 12:01	12.0	347	11.8
B06	05/12/11 12:03	05/12/11 23:32	18.0	689	10.0
B07	05/12/11 23:40	05/13/11 09:30	17.0	590	9.4
B08	05/13/11 09:35	05/13/11 16:34	14.0	419	11.3
B09	05/13/11 16:45	05/13/11 22:36	11.0	351	11.5
B10	05/13/11 22:39	05/14/11 10:41	21.5	722	9.7
B11	05/14/11 10:47	05/14/11 17:08	13.0	381	8.6
B12	05/14/11 17:15	05/14/11 22:42	10.5	327	9.4
B13	05/14/11 22:45	05/15/11 09:23	21.0	638	4.8
B14	05/15/11 09:30	05/15/11 14:27	11	297	2.7
B15	05/15/11 14:31	05/15/11 21:42	8.0	431	3.3
B16	05/15/11 24:46	05/16/11 08:50	10.0	664	8.7

Figure 1. Response of A549 cells to collected ambient samples. Results are
compared to varying concentrations of TiO₂ (right bars)

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

Publications Views
Other subproject views:	All 13 publications	11 publications in selected types	All 10 journal articles
Other center views:	All 191 publications	157 publications in selected types	All 144 journal articles

Publications
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 Exit
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)	Abstract from PubMed Abstract: Taylor and Francis-Abstract Exit
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 Abstract: Taylor&Francis-Abstract Exit
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)	Full-text from PubMed 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)	Abstract from PubMed Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
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)	Abstract from PubMed Abstract: Taylor & Francis-Abstract Exit
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)	Abstract from PubMed 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, Scientific Discipline, Health, PHYSICAL ASPECTS, Air, particulate matter, Genetics, Health Risk Assessment, Risk Assessments, Physical Processes, Biology, altered gene expression, atmospheric particulate matter, long term exposure, atmospheric particles, airway disease, exposure, ambient particle health effects, human exposure, atmospheric aerosol particles, PM, aersol particles

Progress and Final Reports:

Original Abstract

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

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The 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.