1999 Progress Report: Mechanism of PM-Induced Acute Health Effects

EPA Grant Number: R826244
Title: Mechanism of PM-Induced Acute Health Effects
Institution: New York University Medical Center
EPA Project Officer: Chung, Serena
Project Period: January 23, 1998 through January 22, 2001
Project Period Covered by this Report: January 23, 1998 through January 22, 1999
Project Amount: $600,799
RFA: Health Effects and Exposures to Particulate Matter and Associated Air Pollutants (1997) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air , Health Effects


The objective of this study is to determine the biological mechanism for systemic effects associated with acute exposure to ambient particulate matter (PM). We have hypothesized that inhaled PM causes immediate effects on the autonomic regulation of the cardiovascular system resulting in a stress response, and that the biological changes associated with this response can explain a substantial portion of the mortality associated with acute exposure to PM. Our preliminary studies have demonstrated that concentrated ambient PM induces a stress response in normal rats. We will determine whether environmentally relevant concentrations of PM cause a stress response and whether there is a threshold concentration below which PM does not cause acute cardiovascular changes. Moreover, because epidemiologic evidence that PM-associated adverse effects may occur in those individuals with preexisting illness, we have also hypothesized that concentrated ambient PM will produce these systemic effects at lower concentrations in an animal model of compromised health. Because of the confounding effects of gaseous co-pollutants on estimates of relative risk of morbidity and mortality attributable to PM exposure, we will test the hypothesis that ozone and sulfur dioxide alter the stress response to inhaled PM. Finally, because there is uncertainty as to the relative contribution of indoor versus outdoor PM to adverse health effects, we also will examine the dose-response curves for concentrated indoor and outdoor PM.

Progress Summary:

We have demonstrated that the cardiovascular changes produced by exposure to concentrated ambient PM do not occur in rodents on all exposure days. These findings were observed in rodents equipped with EKG transmitters and repeatedly exposed to ambient particles concentrated from New York City air. To reduce the confounding influence of co-pollutants, both ozone and sulfur dioxide were removed from the exposure atmosphere. These results suggest that the adverse effects of PM may be strongly influenced by the day-to-day variation in particle composition. We also have determined that exposure to relatively high levels of concentrated ambient PM does not alter pulmonary function in guinea pigs, rats, and hamsters. We also have begun to examine the genetic susceptibility of rodents to inhaled PM by observing the pulmonary effects of concentrated ambient PM in two inbred strains of mice. No lavage fluid parameters were changed by exposure to concentrated ambient PM, although cytokine mRNA expression was altered (collaboration with Dr. Mossman, University of Vermont).

Future Activities:

As determined so far, concentrated ambient PM has not produced biologically significant adverse health effects in the compromised animal models used to date. We will, therefore, focus our next set of studies on the possible adverse effects of PM in spontaneously hypertensive rats and the role of genetic susceptibility in the response to particles.

Journal Articles on this Report : 3 Displayed | Download in RIS Format

Other project views: All 9 publications 4 publications in selected types All 4 journal articles
Type Citation Project Document Sources
Journal Article Gordon T, Reibman J. Cardiovascular toxicity of inhaled ambient particulate matter. Toxicological Sciences 2000;56(1):2-4. R826244 (1999)
R826244 (2000)
R826244 (Final)
R827351 (Final)
R827351C004 (2002)
R827351C004 (Final)
  • Abstract from PubMed
  • Full-text: Oxford Journals-Full Text HTML
  • Abstract: Oxford Journals-Abstract
  • Other: Oxford Journals-Full Text PDF
  • Journal Article Shukla A, Timblin C, BeruBe K, Gordon T, McKinney W, Driscoll K, Vacek P, Mossman BT. Inhaled particulate matter causes expression of nuclear factor (NF)-κB–related genes and oxidant-dependent NF-κB activation in vitro. American Journal of Respiratory Cell and Molecular Biology 2000;23(2):182-187. R826244 (1999)
    R826244 (2000)
    R826244 (Final)
  • Abstract from PubMed
  • Full-text: AJRCMB-Full Text HTML
  • Abstract: AJRCMB-Abstract
  • Other: AJRCMB-Full Text PDF
  • Journal Article Timblin C, BeruBe K, Churg A, Driscoll K, Gordon T, Hemenway D, Walsh E, Cummins AB, Vacek P, Mossman B. Ambient particulate matter causes activation of the c-jun kinase/stress-activated protein kinase cascade and DNA synthesis in lung epithelial cells. Cancer Research 1998;58(20):4543-4547. R826244 (1999)
    R826244 (Final)
  • Abstract from PubMed
  • Full-text: CancerResearch-Full Text PDF
  • Abstract: CancerResearch-Abstract
  • Supplemental Keywords:

    particles, metals, ambient air, animal, mechanisms., RFA, Health, Scientific Discipline, Air, particulate matter, Toxicology, Health Risk Assessment, Risk Assessments, Biochemistry, Environmental Monitoring, Atmospheric Sciences, co-factors, copollutant exposures, cardiopulmonary responses, inhalability, morbidity, cardiovascular vulnerability, dose response, air pollution, air sampling, biological mechanisms, cardiopulmonary mechanisms, chronic health effects, particulate exposure, Acute health effects, mortality

    Progress and Final Reports:

    Original Abstract
  • 1998
  • Final Report