Final Report: Oxidative Stress Responses to PM Exposure in Elderly Individuals With Coronary Heart Disease

EPA Grant Number: R832413C004
Subproject: this is subproject number 004 , established and managed by the Center Director under grant R832413
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Southern California Particle Center
Center Director: Froines, John R.
Title: Oxidative Stress Responses to PM Exposure in Elderly Individuals With Coronary Heart Disease
Investigators: Delfino, Ralph , Gastanaga, Victor , Gillen, Dan , Neuhausen, Susan , Staimer, Norbert , Vaziri, Nosratola D
Institution: University of California - Irvine
EPA Project Officer: Chung, Serena
Project Period: October 1, 2005 through September 30, 2010 (Extended to September 30, 2012)
RFA: Particulate Matter Research Centers (2004) RFA Text |  Recipients Lists
Research Category: Health Effects , Air

Objective:

The overall goal of this study was to advance knowledge on the importance of particle size and composition to the induction of oxidative stress responses. Project 4 was a cohort panel study with repeated measures of outcomes and exposures in 60 elderly subjects with a history of coronary artery disease. We hypothesized that circulating biomarkers of systemic responses related to oxidative stress (in up to 12 weekly blood samples) would be associated with exposure to indoor and outdoor home PM mass and total particle number concentration. Given the interplay between oxidative stress and inflammation, we anticipated this would support the view that PM leads to systemic inflammatory responses and adverse impacts on cardiovascular function (also measured in subjects). We further hypothesized that biomarkers would be more strongly associated with predicted indoor exposure to PM of outdoor origin (from source tracer analyses). We also evaluated effects of exposure to specific metals, elemental and organic carbon, estimates of primary and secondary organic aerosol fractions of PM, and specific organic components in PM that we used as source tracers. We further hypothesized that biomarker associations with ultrafine and fine PM would be better explained by an in vitro assay of PM oxidative potential. Individual susceptibility was also assessed, including medication use and polymorphisms in genes coding for proteins involved in oxidative stress responses.

Summary/Accomplishments (Outputs/Outcomes):

Project 4 investigators prospectively followed a cohort panel of elderly people with coronary artery disease living in retirement communities of the Los Angeles air basin. They found positive associations of circulating biomarkers of inflammation and platelet activation in plasma with both quasi-ultrafine particle mass and markers of exposures linked to fossil fuel combustion (including PM2.5 carbonaceous aerosols), but not with transition metals, secondary (photochemically-related) organic carbon or ozone. In a majority subset of this panel, they also found that erythrocyte antioxidant enzyme activities decreased with exposure to the same air pollutants. Since the erythrocyte antioxidant enzymes were also inversely associated with circulating biomarkers of inflammation, it is possible that enzyme inactivation may play a role in the pro-inflammatory effects of air pollutants. Using a parallel set of indoor and outdoor home air pollutant measurements they showed that associations of systemic biomarkers with outdoor PM are consistent with associations for indoor exposures to PM of outdoor origin. This supports the view that adverse health effects of outdoor air pollutants occur even though people spend most of their time indoors. In vitro work from Projects 3 and 4 suggest that particle electrophilic potential can lead to the irreversible inactivation of protein function, including antioxidant enzymes. A follow-up analysis in Project 4 found that the PAH fraction of quasi-ultrafine particles explained associations of biomarkers of inflammation with quasi-ultrafine mass. PAH was linked to combustion emissions from traffic using chemical mass balance model that included hopanes (vehicle emissions tracer). Interestingly, markers of secondary organic aerosols in quasi-ultrafine particles (water-soluble carbon and n-alkanoic acids) were not associated with circulating biomarkers of inflammation, but were associated with the fractional concentration of exhaled nitric oxide, which is a biomarker of airway inflammation. This suggests that different particle components affect different target organs likely due to differing toxicokinetics. Biomarkers of both systemic and airway inflammation were associated with the in vitro oxidative potential of quasi-ultrafine particles to induce rat alveolar macrophages to produce reactive oxygen species, and this was not explained by the mass concentration of quasi-ultrafine particles. In the same panel, Project 4 investigators found significant and large increases in systolic and diastolic blood pressure in relation to PM2.5 mass, black carbon, and primary organic carbon exposures.  Blood pressure was more weakly associated with secondary organic carbon, and was not associated with ozone. In a parallel analysis of ambulatory electrocardiograph data from 38 of the subjects in the panel, Project 4 investigators found significant associations between the risk of ST segment depression ³1.0 mm with exposure to quasi-ultrafine particles and markers of primary products of fossil fuel combustion. ST segment depression was not associated with PM2.5, secondary organic carbon or ozone.  These results suggest that primary products of fossil fuel combustion lead to an increased risk of myocardial ischemia. 

 

Analysis of the relationship of biomarkers of inflammation and antioxidant activity with exposure to PM air pollution:

The primary research focus of the NIH, NIEHS-funded parent study (R01 ES-012243) was on the varying effects of different particle size fractions (including particles < 0.25 µm) on a plasma biomarker of platelet activation, soluble platelet selectin (sP-selectin) and plasma biomarkers of systemic inflammation, including interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a) and its receptor-II (sTNF-RII), and C-reactive protein (CRP). In Project 4, this work was expanded to more comprehensively evaluate relative differences in association between primary organic aerosols (POA) vs. secondary organic aerosols (SOA). We found that exposure markers of POA and SOA have different spatial and temporal variability and they are thus minimally or uncorrelated in the study region (Arhami et al. 2010; Delfino et al. 2008, 2009, 2010a).  We first assessed differences in association from primary vs. secondary organic aerosols by using two fractions of total organic carbon (OC) in PM2.5 that were estimated to represent primary and secondary sources. These were primary OC and secondary OC, respectively (Polidori et al. 2007). In the regression analysis of data from the follow-up of four panel groups over two years (Delfino et al. 2009, 2010a), we confirmed our earlier findings for the first of two years of data (Delfino et al. 2008). In mixed regression models controlling for temperature, community, and season, we found many positive associations of circulating biomarkers with markers of pollutant particles from the primary combustion of fossil fuels (primary OC, elemental carbon, black carbon, particle number, PAH, and hopanes) and as well as related gases (CO and NOx). This included biomarkers of systemic inflammation (IL-6, TNF-a, sTNF-RII, and CRP) and platelet activation (sP-selectin). Association were, in general, stronger for quasi-ultrafine particles < 0.25 µm as compared with PM 0.25-2.5 µm and 2.5-10 µm in aerodynamic diameter. Associations with secondary OC and other markers of SOA (water-soluble organic carbon and n-alkanoic acids) were weaker than with markers of POA and were nonsignificant.  This null effect contributed to weaker associations for total OC. These findings strongly suggest that associations of PM with systemic outcomes were attributable to primary combustion aerosols (largely from vehicular traffic in the LA basin). Transition metals in quasi-ultrafine particles (from various sources throughout the basin) were not associated with the circulating biomarkers.

We also evaluated pollutant associations with 12 weekly offline measurements of fractional exhaled nitric oxide (FeNO), which is a marker of airway inflammation (Delfino et al. 2010c). FeNO was measured offline using procedures recommended by the American Thoracic Society and European Respiratory Society. We found FeNO was associated only with markers of SOA, with O3, and with PM0.25-2.5, which is enriched in SOA. In complete contrast, recall that IL-6 was associated only with markers of POA, especially total PAH, with PM0.25, which is enriched in POA, and with pollutant gases that are markers of fossil fuel combustion (CO, and NOx). Furthermore, FeNO was not significantly associated with any of the blood biomarkers.  These results suggest that different pollutant components have different pro-inflammatory effects on respiratory and systemic targets.

Additionally, a key aim of Project 4 was to evaluate the activities of two critically important erythrocyte antioxidant enzymes [glutathione peroxidase-1 (GPx-1) and Cu,Zn-superoxide dismutase (Cu,Zn-SOD)] in the up to 12 weekly blood samples from each of the study subjects. In regression analyses we found inverse associations of air pollutants (especially quasi-ultrafine particles and markers of POA) with GPx-1 and Cu,Zn-SOD activities (Delfino et al. 2008, 2009). Additional analysis of GPx-1 and Cu,Zn-SOD in relation to exposures to chemical components in quasi-ultrafine particles (Delfino et al. 2010a) showed regression coefficients for PM components (PAH and hopanes) were largely negative suggesting inverse associations with erythrocyte antioxidant enzymes (CuZn-SOD and GPx-1), but most upper confidence limits crossed 1.0 (Delfino et al. 2010a). An exploratory analysis showed that among seven subjects previously identified as a “positive responder group” (Delfino et al. 2009) we found largely positive associations of CuZn-SOD and GPx-1 with air pollutants, and lower confidence limits were >1.0 for outdoor PM0.25 mass and several other exposures.  In the 53 subjects previously identified as a “negative responder group,” we found inverse associations of CuZn-SOD and GPx-1 with markers of exposures linked to primary combustion, including hopanes (vehicle emissions tracer), and indoor and outdoor total PAH as well as low, medium and high molecular weight PAH. Indoor water-soluble organic carbon was inversely (p < 0.07) associated with CuZn-SOD, but there were no other associations with SOA markers in the negative responder group, including n-alkanoic acids. Transition metals were not associated with either CuZn-SOD or GPx-1.  

The erythrocyte antioxidant enzymes were also inversely associated with circulating biomarkers of inflammation and platelet activation.  Therefore, pollutant associations with antioxidant enzymes may at least in part be related to our findings of significantly increased markers of platelet activation and inflammation in relation to exposures to combustion-related air pollutants (e.g., elemental carbon and primary organic carbon) (Delfino et al. 2008, 2009, 2010a, 2010c).  The importance of combustion-related chemicals is supported by our finding that associations of plasma IL-6 and TNF-RII with PM0.25 mass were completely confounded by the PAH fraction of PM0.25, and these cytokine biomarkers were not associated with chemical tracers of SOA (Delfino et al. 2010a).  Our chemical mass balance model results using source tracers showed that a majority of the PAH came from vehicular sources (Arhami et al. 2010; Delfino et al. 2010a).  This suggests that chemical components from traffic are responsible for blood biomarker associations with uncharacterized quasi-ultrafine particle mass.

Relationship of biomarkers of inflammation to ROS production by PM using an in vitro bioassay of aqueous particle extracts:

We additionally evaluated the relation of airway and systemic inflammatory responses to the potential of aqueous extracts of the weekly PM0.25 filters to induce cellular production of ROS (Delfino et al. 2010c). As a marker of PM oxidative potential, ROS production was measured by exposing rat alveolar macrophages (NR8383) in vitro to the aqueous extracts of PM0.25 collected outdoors at the subjects’ retirement community. Health outcomes in regression analyses included 12 weekly measurements of both plasma IL-6 (a biomarker of systemic inflammation) and FeNO (a biomarker of airway inflammation) in the 60 elderly subjects studied previously (Delfino et al. 2009, 2010a). Both IL-6 and FeNO were associated with the oxidative potential of quasi-ultrafine particles to induce macrophages to produce reactive oxygen species. Results from regression models including both PM0.25 mass with ROS production showed that oxidative potential explained most of the association of IL-6 with PM0.25 mass. The association of FeNO with ROS activity was not reflected by PM0.25 mass concentration at all. We concluded that the ability of particles to induce ROS generation by macrophages is associated with both systemic and airway biomarkers of inflammation and that these associations are nominally reflected by particle mass concentration.

Analysis of cardiovascular function:

As part of the NIH, NIEHS-funded parent study (R01 ES-012243) we analyzed the relation of air pollutant exposures to both hourly blood pressure and from ambulatory blood pressure monitors and ST depression ³1 mm (indicative of cardiac ischemia) from continuous from ambulatory electrocardiographs (both over 10 days). Both outcomes were collected using ambulatory monitors over a 10-day period in each of the study subjects. Complementary results from PM Center work established coherence with the blood biomarker data by estimating relative effects from particle size fractions and from POA vs SOA markers. Briefly, we found significant positive associations of systolic and diastolic blood pressure with air pollutants in mixed regression models controlling for temperature, community, and season (Delfino et al. 2010b). The strongest associations were with PM2.5 OC as compared with PM2.5 black carbon or PM2.5 mass.  Associations also strengthened with longer multi-day averaging time to nine days. Effect estimates were clinically relevant. For example, an interquartile range increase (25th to 75th percentile) in 5-day average OC (5.2 µg/m3) was associated with 6.0 mm Hg higher mean systolic blood pressure (95% CI: 1.0, 11) and 4.6 mm Hg higher mean diastolic BP (95% CI: 1.9, 7.2). An analysis of the OC fraction showed that primary OC was more strongly associated with blood pressure than secondary OC, which was a significant relation. These results suggest that exposure to primary organic components of fossil fuel combustion near the home are strongly associated with increased ambulatory blood pressure in a population at potential risk of myocardial infarction. Results also showed that secondary OC was associated with BP, perhaps though an effect on airways given the findings for FeNO

While wearing the ambulatory blood pressure monitor, each subject was also followed for 10 days with 24-hr ambulatory electrocardiograph monitors (Holter monitors). Generalized estimating equations were used to estimate the odds of ST segment depression ³1 mm (indicative of possible ischemia) from hourly exposure to air pollution controlling for temperature, community, and season.  We found significant positive associations of ST segment depression events with markers of primary combustion aerosols, including primary OC and black carbon, but not secondary OC. Associations were stronger for multiday averages and for the 92% of time that subjects were at home near the air monitors. 

Overall our results show that biomarkers of systemic inflammation (Delfino et al. 2009, 2008, 2010a, in press), ambulatory blood pressure (Delfino et al. 2010b), and electrocardiographic ST segment depression ³1 mm (Delfino et al. submitted) are more strongly associated with POA than SOA exposure markers (and related chemical components). Findings indicate that traffic-related pollutants, the predominant source of POA in many urban areas, have adverse cardiovascular effects that could include cardiac ischemia. This is in contrast with our finding that a biomarker of airway inflammation (fractional exhaled NO) was much more strongly associated with SOA and ozone, than with POA or combustion-related gases (CO or NOx) (Delfino et al. 2010c).  It is possible that many hydrophilic and highly oxidized SOA chemical components have immediate pro-oxidant effects on the airways, whereas many POA components (e.g., PAH), are hydrophobic and require biotransformation to pro-oxidant species after systemic distribution via the circulation. A commonly assumed pathway to the systemic inflammatory effects of particulate air pollution is the activation of leukocytes in the lungs, followed by the release of pro-inflammatory mediators. Our epidemiologic findings do not support this as a major mechanism, but experimental work as well as additional studies in human populations is needed to evaluate this issue.

In vitro assay of antioxidant enzyme inactivation:

To follow-up on the findings of the inverse associations of primary pollutants with the activity of the antioxidant enzyme GPx-1 in the cohort panel, we developed a high-throughput assay for investigating the inhibitory properties of electrophilic compounds and other components (present in air and air particulate suspensions) on GPx-1 (Staimer et al. 2012). This in vitro test provides a biomonitoring tool for in vivo studies. We developed a rapid assay that has shown positive results using a number of electrophilic compounds (including acrolein, crotonaldehyde, and benzoquinone) with immobilized erythrocyte GPx-1 as a probe. The immobilization of GPx to the wells of a microtiter plate enables us to remove the reactive compounds simply by washing before adding the substrate mixture. We also used this assay as a preliminary test of aqueous extracts of particles from filter samples as well as diesel exhaust particles. Briefly, using air samples collected at a heavily trafficked urban area of Los Angeles collected at the USC Particle Instrumentation Unit, we found a direct inhibitory effect of aqueous particle filter extracts on the activity of GPx-1. Similar effects were found for diesel exhaust particles. These findings indirectly suggest that traffic-related air pollutants have the potential to generate oxidative stress by electrophile-derived covalent modifications of enzymes involved in the cytosolic defense against reactive oxygen and nitrogen species.

Assessment of oxidative stress using carbonylated proteins:

We used the OxiSelect™ Protein Carbonyl ELISA kit (Cell Biolabs, Inc., San Diego, CA) for the rapid detection and quantification of protein carbonyls in plasma samples. We measured the protein carbonyl concentrations (nmol/mg) for year two samples in 31 subjects (312 samples assayed in duplicate). Analysis of plasma protein carbonyl concentration as a marker of oxidative stress in relation to air pollutant measurements was conducted for the year two samples using mixed models as described for the other biomarkers. There were no associations between this biomarker and any of the air pollutants. As a result, we decided that this was not an informative biomarker and the assay of year 1 samples was not done. We also found no association between protein carbonyls and GPx-1 or Cu,Zn-SOD. 

Ethane and n-Pentane in Exhaled Breath: Biomarkers of Oxidative Stress or just Exposure?

Briefly, we tested whether exhaled ethane or n-Pentane in were biomarkers of exposure as opposed to biomarkers of effect, namely oxidative stress as previously claimed. In this study (Gorham et al. 2009), 16 elderly subjects from the Riverside retirement community were followed over 12 weeks and their exhaled breath was analyzed using canister sampling and GC/GC-MS analysis that has been developed by the UCI Department of Chemistry, Rowland-Blake research group. End expiratory air was collected to avoid contamination with room air and we subtracted room ethane and n-pentane from exhaled breath concentrations (residual levels were slightly positive). Exhaled hydrocarbon concentrations were normalized to exhaled CO2.  FeNO was used as a biomarker of airway inflammation and plasma carbonylated proteins was used as a marker of systemic oxidative stress (both measured as described above). Statistical analyses were performed using mixed models to investigate the within-subject relation of the inflammatory and oxidative stress biomarkers with the breath hydrocarbons. In addition, we tested the relationship between the breath hydrocarbons and indoor and outdoor gaseous air pollutants (NO, NO2, and CO).

We found that hydrocarbon concentrations in breath were correlated with room air hydrocarbon samples (R2 = 0.93 and 0.74, for ethane and n-pentane, respectively). Mixed model analysis of adjusted exhaled concentrations of ethane and n-pentane from elderly subjects did not show significant associations with FeNO. Additionally, neither of the exhaled hydrocarbons had positive associations with carbonylated proteins measured in the blood. Finally, positive but weak associations between measurements of exhaled hydrocarbons (ethane and n-pentane) and air pollutants (NOx, and CO) were observed in mixed model analyses. Exposure to gaseous air pollutants had a weak but significant impact on exhaled ethane and n-pentane possibly secondary to residual ethane and n-pentane in the airways not adjusted for by subtracting room ethane and n-pentane from exhaled breath concentrations. It is likely that these hydrocarbon gases are positively correlated with criteria pollutant gases in both outdoor and indoor environments of the subjects. Therefore, it is possible that the association reflects exposure to air pollutant mixtures. We conclude that exhaled ethane and n-pentane are not markers of oxidative stress or airway inflammation, but instead are markers of previous exposure to air pollutants.

Assessment of gene-environment interactions:

We conducted genotyping for the glutathione S-transferase M1 (GSTM1) gene located on chromosome 1p13.3. The homologous recombination between two almost identical 4.2 Kb regions flanking the GSTM1 gene results in a 16Kb deletion containing the entire gene. It is referred to as a null allele of the GSTM1 gene. Similarly, the null allele was reported in the glutathione S-transferase T1 (GSTT1) gene. The protein products of GSTM1 and GSTT1 are key enzymes involved in oxidative stress responses.  For both of these genes, the presence of homozygous null alleles leads to a lack of function in the enzyme. Out of 60 subjects genotyped, we found 29 subjects (48%) were homozygous GSTM1 null, and 7 subjects (12%) were homozygous GSTT1 null. We found little to no evidence for effect modification by either GSTM1 or GSTT1 null genotypes for relations between air pollutant exposures and a key biomarker of inflammation (IL-6) or the two erythrocyte antioxidant enzymes (Cu,Zn-SOD and GPx-1).

Conclusions:

Overall, these significant findings for quasi-ultrafine particles and markers of traffic-related particles support the hypothesis that redox-active and other particle components from the combustion of fossil fuel directly affect cardiovascular target sites resulting in systemic inflammation and platelet activation. As a possible result of this and other mechanisms, these same exposures are significantly associated with adverse cardiovascular responses including increased blood pressure and electrocardiographic evidence of cardiac ischemia.


Journal Articles on this Report : 12 Displayed | Download in RIS Format

Other subproject views: All 35 publications 15 publications in selected types All 15 journal articles
Other center views: All 241 publications 157 publications in selected types All 157 journal articles
Type Citation Sub Project Document Sources
Journal Article Arhami M, Polidori A, Delfino RJ, Tjoa T, Sioutas C. Associations between personal, indoor, and residential outdoor pollutant concentrations:implications for exposure assessment to size-fractionated particulate matter. Journal of the Air & Waste Management Association 2009;59(4):392-404. R832413 (2009)
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  • Journal Article Arhami M, Minguillon MC, Polidori A, Schauer JJ, Delfino RJ, Sioutas C. Organic compound characterization and source apportionment of indoor and outdoor quasi-ultrafine particulate matter in retirement homes of the Los Angeles Basin. Indoor Air 2010;20(1):17-30. R832413 (2009)
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  • Journal Article Delfino RJ, Staimer N, Tjoa T, Polidori A, Arhami M, Gillen DL, Kleinman MT, Vaziri ND, Longhurst J, Zaldivar F, Sioutas C. Circulating biomarkers of inflammation, antioxidant activity, and platelet activation are associated with primary combustion aerosols in subjects with coronary artery disease. Environmental Health Perspectives 2008;116(7):898-906. R832413 (2007)
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  • Journal Article Delfino RJ, Staimer N, Tjoa T, Gillen DL, Polidori A, Arhami M, Kleinman MT, Vaziri ND, Longhurst J, Sioutas C. Air pollution exposures and circulating biomarkers of effect in a susceptible population: clues to potential causal component mixtures and mechanisms. Environmental Health Perspectives 2009;117(8):1232-1238. R832413 (2009)
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  • Journal Article Delfino RJ, Staimer N, Tjoa T, Arhami M, Polidori A, Gillen DL, Kleinman MT, Schauer JJ, Sioutas C. Association of biomarkers of systemic inflammation with organic components and source tracers in quasi-ultrafine particles. Environmental Health Perspectives 2010;118(6):756-762. R832413 (Final)
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  • Journal Article Delfino RJ, Tjoa T, Gillen DL, Staimer N, Polidori A, Arhami M, Jamner L, Sioutas C, Longhurst J. Traffic-related air pollution and blood pressure in elderly subjects with coronary artery disease. Epidemiology 2010;21(3):396-404. R832413 (2009)
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  • Journal Article Delfino RJ, Staimer N, Tjoa T, Arhami M, Polidori A, Gillen DL, George SC, Shafer MM, Schauer JJ, Sioutas C. Associations of primary and secondary organic aerosols with airway and systemic inflammation in an elderly panel cohort. Epidemiology 2010;21(6):892-902. R832413 (Final)
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  • Journal Article Delfino RJ, Gillen DL, Tjoa T, Staimer N, Polidori A, Arhami M, Sioutas C, Longhurst J. Electrocardiographic ST-segment depression and exposure to traffic-related aerosols in elderly subjects with coronary artery disease. Environmental Health Perspectives 2011;119(2):196-202. R832413 (Final)
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  • Journal Article Delfino RJ, Staimer N, Vaziri ND. Air pollution and circulating biomarkers of oxidative stress. Air Quality, Atmosphere & Health 2011;4(1):37-52. R832413 (Final)
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  • Journal Article Gorham KA, Sulbaek Andersen MP, Meinardi S, Delfino RJ, Staimer N, Tjoa T, Rowland FS, Blake DR. Ethane and n-pentane in exhaled breath are biomarkers of exposure not effect. Biomarkers 2009;14(1):17-25. R832413 (Final)
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  • Journal Article Polidori A, Cheung KL, Arhami M, Delfino RJ, Schauer JJ, Sioutas C. Relationships between size-fractionated indoor and outdoor trace elements at four retirement communities in southern California. Atmospheric Chemistry and Physics 2009;9(14):4521-4536. R832413 (2009)
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  • Journal Article Staimer N, Nguyen TB, Nizkorodov SA, Delfino RJ. Glutathione peroxidase inhibitory assay for electrophilic pollutants in diesel exhaust and tobacco smoke. Analytical and Bioanalytical Chemistry 2012;403(2):431-441. R832413 (Final)
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  • Supplemental Keywords:

    Health Effects, Human health, Sensitive populations, Dose-response, Enzymes, Particulates, Epidemiology, Environmental chemistry, Modeling., RFA, Health, Scientific Discipline, Air, particulate matter, Health Risk Assessment, Risk Assessments, Biochemistry, Ecology and Ecosystems, atmospheric particulate matter, particulates, elderly adults, human health effects, PM 2.5, airway disease, airborne particulate matter, cardiovascular vulnerability, air pollution, human exposure, vascular dysfunction, cardiovascular disease, human health risk

    Progress and Final Reports:

    Original Abstract
  • 2006 Progress Report
  • 2007 Progress Report
  • 2008 Progress Report
  • 2009 Progress Report
  • 2010 Progress Report
  • 2011

  • Main Center Abstract and Reports:

    R832413    Southern California Particle Center

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R832413C001 Contribution of Primary and Secondary PM Sources to Exposure & Evaluation of Their Relative Toxicity
    R832413C002 Project 2: The Role of Oxidative Stress in PM-induced Adverse Health Effects
    R832413C003 The Chemical Properties of PM and their Toxicological Implications
    R832413C004 Oxidative Stress Responses to PM Exposure in Elderly Individuals With Coronary Heart Disease
    R832413C005 Ultrafine Particles on and Near Freeways