Grantee Research Project Results
2003 Progress Report: Health Effects of Airborne Particulate Matter and Gasses
EPA Grant Number: R829215Title: Health Effects of Airborne Particulate Matter and Gasses
Investigators: Pinkerton, Kent E. , Kennedy, Ian M. , Lighty, JoAnn S , Buckpitt, Alan , Aust, Ann , Veranth, John
Current Investigators: Pinkerton, Kent E. , Kennedy, Ian M. , Aust, Ann , Veranth, John , Leppert, Valerie
Institution: University of California - Davis , Utah State University , University of Utah
Current Institution: University of California - Davis , University of California - Merced , University of Utah , Utah State University
EPA Project Officer: Chung, Serena
Project Period: October 1, 2001 through September 30, 2004 (Extended to September 30, 2005)
Project Period Covered by this Report: October 1, 2002 through September 30, 2003
Project Amount: $833,481
RFA: Health Effects of Particulate Matter (2001) RFA Text | Recipients Lists
Research Category: Air Quality and Air Toxics , Nanotechnology , Human Health , Particulate Matter , Air
Objective:
The objective of this research project is to examine the mechanisms of particulate toxicity in the lungs of neonatal rats following short (1-3 days) and long-term (28 days) exposure to iron/soot or coal fly ash particles in the presence or absence of ozone. Specifically, we will examine effects that directly impact epithelial cells of the neonatal airways, centriacinar regions, and alveoli. Because epithelial cells are the first cells in the respiratory tract to come into contact with inhaled particles, we hypothesize that damage to these cells can serve as a direct and highly sensitive measure of particle toxicity. We hypothesize that epithelial cells lining the transitional zone between the airways and gas exchange regions of the lungs (i.e., the central acinus) are particularly sensitive and play a key role in the initiation and progression of particle-induced pulmonary injury. We further hypothesize that epithelial-particle interactions initiate a cascade of events that underlie the adverse effects associated with inhaled particles. We hypothesize that particle toxicity (in the presence of a transition metal—iron) begins with the depletion of cellular glutathione levels in epithelial cells, thus accentuating the cytotoxic events leading to cell death. In turn, cell death begins the process of cellular proliferation. Each of these events impacts negatively the ability of the lungs to translocate and clear particles, thus leading to further irritation and injury. We will test each of these hypotheses using novel approaches to examine epithelial cell structure and function throughout the airways and alveoli.
Progress Summary:
During the current progress period, we have examined in detail the characteristics of iron and soot particles generated under experimental conditions for inhalation studies. This characterization has been instrumental in describing the generation of combustion particles under controlled conditions. To study their influence on early postnatal development, a simple, laminar diffusion flame was used to generate an aerosol of soot and iron particles in the size range of 10 to 50 nm. Exposure of 10-day-old rat pups to particles of soot and iron was for 6 hours per day for 3 days. The lungs were examined following a single injection of bromodeoxyuridine 2 hours before necropsy. Neonatal rats exposed to these particles demonstrated no effect on the rate of cell proliferation within terminal bronchioles or the general lung parenchyma. In contrast, within those regions arising immediately beyond the terminal bronchioles (defined as the proximal alveolar region), the rate of cell proliferation was significantly reduced compared with filtered air controls. These findings strongly suggest that exposure to airborne particles during early neonatal life has significant direct effects on lung growth by altering cell division within critical sites of the respiratory tract during periods of rapid postnatal development. Such effects may result in altered growth in the respiratory system that may be associated with lifelong consequences.
Future Activities:
We will conduct new experiments to further examine the health effects of sustained exposure to airborne iron and soot particles in both neonatal animals as well as young adult animals. Our plans are to systematically examine the effects of ultrafine particles on cell proliferation and maturation during critical windows of development in the neonatal rat. These studies will include exposures during the first 3 weeks of life. Our plan is to target specific 3-day periods in neonatal rats of rapid cell proliferation with the formation of new alveoli. We also plan to conduct more extended studies to follow prolonged particle exposure of the newborn rat (to iron and soot particles) from birth to 3 weeks of age. This period of time in the life of the rat constitutes the most critical period of postnatal lung development, with the formation of new alveoli, rapid cell proliferation, and expansion of existing alveoli to adult levels. Our studies with young adult animals are designed to examine not only local measures of oxidative stress within the lungs, but also systemic markers of oxidative stress that may prove useful in better monitoring particulate matter effects using noninvasive approaches to measure these effects.
Journal Articles on this Report : 3 Displayed | Download in RIS Format
Other project views: | All 23 publications | 15 publications in selected types | All 15 journal articles |
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Pinkerton KE, Zhou Y-M, Teague SV, Peake JL, Walther RC, Kennedy IM, Leppert VJ, Aust AE. Reduced lung cell proliferation following short-term exposure to ultrafine soot and iron particles in neonatal rats: key to impaired lung growth? Inhalation Toxicology 2004;16(Suppl 1):73-81. |
R829215 (2003) R829215 (2004) R829215 (Final) R827995 (Final) |
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Zhou Y-M, Zhong C-Y, Kennedy IM, Pinkerton KE. Pulmonary responses of acute exposure to ultrafine iron particles in healthy adult rats. Environmental Toxicology 2003;18(4):227-235. |
R829215 (2003) R829215 (2004) R829215 (Final) R826246 (Final) R827995 (Final) |
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Zhou Y-M, Zhong C-Y, Kennedy IM, Leppert VJ, Pinkerton KE. Oxidative stress and NFκB activation in the lungs of rats: a synergistic interaction between soot and iron particles. Toxicology and Applied Pharmacology 2003;190(2):157-169. |
R829215 (2003) R829215 (2004) R829215 (Final) R827995 (Final) |
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Supplemental Keywords:
children's health, airborne particles, pulmonary system, lungs, ozone, neonatal rats, epithelial cells, particle toxicity, airborne particulate matter, airborne particulate matter, gas, iron, soot, coal fly ash particles, air pollution., RFA, Health, PHYSICAL ASPECTS, Scientific Discipline, Air, Waste, Ecosystem Protection/Environmental Exposure & Risk, Bioavailability, particulate matter, Health Risk Assessment, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Physical Processes, Disease & Cumulative Effects, Environmental Monitoring, Children's Health, tropospheric ozone, genetic susceptability, Incineration/Combustion, Immunology, health effects, particulates, ambient air quality, urban air, PM10, sensitive populations, coal fly ash particles, neonates, PM 2.5, air pollutants, effects assessment, neonatal rats, lead, ozone, exposure, ambient measurement methods, ambient air, alveolar cells, airway disease, pulmonary disease, epithelial cells, children, particles, human exposure, clinical studies, animal models, sensitive subgroups, ecological risk, urban soot, ambient particulates, Acute health effects, allergic response, measurement methods , iron/soot, animal studies, coal fly ash, combustion gases, soot profiles, exposure assessment, human health riskRelevant Websites:
http://www.envtox.ucdavis.edu/cehs/ Exit
http://agcenter.ucdavis.edu/agcenter/ Exit
Progress 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.