The Wise Laboratory of Environmental and Genetic Toxicology

Ambient Particulate Matter

Background | Experimental Studies | References | Wise Laboratory Publications | Collaborators | Funding

Background

Ambient particulate matter (APM) is an airborne mixture of particles. Recently a great deal of public health concern has been raised about the effects of these particles on the lungs and the cardiopulmonary system. APM has been related to pulmonary toxicity for over 40 years (1). However, these concerns have historically taken a backseat to concerns focused on the pulmonary effects of cigarette smoke. It is in the last few years, however that APM has come to the forefront of concern, with many new epidemiological studies from around the world, indicating that as APM levels rise, there is a concomitant rise in: 1) risk of lung cancer 2) emergency room admissions for cardiopulmonary concerns, and 3) cardiopulmonary deaths (2-7). The factors involved in the toxicity of APM remain uncertain.

One of the complicating factors in studying APM is that the particles vary in origin, composition and size. Most APM comes from combustion sources. However, the specific combustion source (e.g. power plant smokestacks, car exhaust etc.) is the major determinate of particle size and composition of the particles. For example, oil combustion produces large amounts of vanadium (V) and nickel (Ni), and petroleum-fueled engines produce lead pollution (8-10).

APM typically consists of a mixture of organic compounds such as polycyclic aromatic hydrocarbons and inorganic compounds including metals like lead, nickel, vanadium and chromium (8-10). The relative amounts of these components, however, will depend on the combustion source as mentioned above. There is no universal standard that defines the amount of each component of APM, nor has an average even been obtained, but APM has been collected from around the world and a range of levels can begin to be defined.

Most studies have focused on the immediate cardiopulmonary effects of APM (11-21). These studies have found that this toxicity is mediated by the metal fraction of the APM (11-13). The metals most commonly found are iron (Fe), vanadium (V), nickel (Ni), cadmium (Cd), chromium (Cr), lead (Pb) and manganese (Mn). These range from relatively high levels for Pb (3-150 ng/m3) and Fe (3-500 ng/m3), to more modest levels for V (2.1-18 ng/m3), Ni ((0.54-11 ng/m3), Cr (0.5-1 ng/m3), and Cd (0.5-1 ng/m3). This finding is provocative, particularly with respect to lung cancer, as 4 metals in APM (Ni, Cr, Cd and arsenic) are classified as known, and 2 others, (Pb and cobalt), are classified as probable human carcinogens by the International Agency for Cancer Research (22). However, despite the epidemiology indicating that APM is a lung carcinogen and evidence that the metals from APM are bioactive, the carcinogenic effects of metals from APM have not been investigated.

Clearly our current knowledge of APM carcinogenicity is inadequate. Our research addresses these critical shortcomings. When completed it will provide: 1) an understanding of how APM causes genetic damage and neoplastic transformation; 2) essential information to better assess the relative risk of exposure to APM; and 3) a model of human lung epithelial cells for further study of particles.

Experimental Studies

Ambient particulate matter is the microscopic dust we breathe in each day as a result of pollution in our air. It has been shown to be a major factor in asthma. The long-term objective of our research has two directions. One is to determine if ambient particulate matter is carcinogenic to human bronchial cells. The second is to investigate the mechanisms by which ambient particulate matter causes or worsens bronchial asthma. This is important because we are exposed to ambient particulate matter and it contains substantial amounts of metals that can accumulate in bronchial cells over a period of years. Currently, there are few data concerning the carcinogenic effects of ambient particulate matter in human bronchial cells. We are focusing on the ability of ambient particulate matter to cause DNA damage and chromosome aberrations. Efforts are also underway to understand how ambient particulate matter signals cells to initiate the inflammatory responses associated with asthma.

APM particles undergoing internalization APM particles inside a vacuole APM particles inside a mitotic cell
This figure shows that APM particles were undergoing initial internalization (arrow). Magnification=21000x This figure shows that APM particles were located within vacuoles (arrow). Magnification=21000x This figure shows that a mitotic cell containing APM particles (arrow).          Magnification=21000x

References

  1. Pike MC, Gordon RJ, Henderson, BE, Menck HR, SooHoo J. (1975) Air pollution. In Fraumeni J (ed.) Persons at High Risk of Cancer. An Approach to Cancer Etiology and Control. Academic Press, New York.
  2. Saldiva PH, Pope CA 3rd, Schwartz J, Dockery DW, Lichtenfels AJ, Salge JM, Barone I, Bohm GM (1995) Air pollution and mortality in elderly people: a time-series study in Sao Paulo, Brazil. Arch Environ Health.50:159-63.
  3. Timonen KL, Pekkanen J (1997) Air pollution and respiratory health among children with asthmatic or cough symptoms. Am J Respir Crit Care Med. 156:546-52.
  4. Lipsett M, Hurley S, Ostro B (1997) Air pollution and emergency room visits for asthma in Santa Clara County, California. Environ Health Perspect. 105:216-22.
  5. Cohen AJ, Pope CA 3rd, Speizer FE (1997) Ambient air pollution as a risk factor for lung cancer. Salud Publica Mex. 39:346-55.
  6. Cohen AJ, Pope CA 3rd (1995) Lung cancer and air pollution. Environ Health Perspect. 103 8:219-24.
  7. Pope CA 3rd, Thun MJ, Namboodiri MM, Dockery DW, Evans JS, Speizer FE, Heath CW Jr (1995) Particulate air pollution as a predictor of mortality in a prospective study of U.S. adults. Am J Respir Crit Care Med. 151:669-74.
  8. Spengler JD and Thurston GD (1983) Mass and Elemental Composition of Fine and Coarse Particulates in Six U.S. Cities J Air Pollut Control Assoc 33:1162-1171.
  9. Bagnoli P, Carrozzino S, Pisani B, Righini F (1997) Chemical characterization of the PM10 fraction of airborne particulate matter in the urban atmosphere. J Environ Pathol Toxicol Oncol 16:219-25.
  10. Ghio AJ, Stonehuerner J, Pritchard RJ, Piantodosi CA, Quigley DR, Dreher KL, Costa DL (1996) Humic-like substances in air pollution particulates correlate with concentrations of transition metals and oxidant generation. Inhal Toxicol 8:479-494.
  11. Dreher KL, Jaskot RH, Lehmann JR, Richards JH, McGee JK, Ghio AJ, Costa DL (1997) Soluble transition metals mediate residual oil fly ash induced acute lung injury. J Toxicol Environ Health. 50(3):285-305.
  12. Carter JD, Ghio AJ, Samet JM, Devlin RB (1997) Cytokine production by human airway epithelial cells after exposure to an air pollution particle is metal-dependent. Toxicol Appl Pharmacol. 146:180-8.
  13. Kodavanti UP, Hauser R, Christiani DC, Meng ZH, McGee J, Ledbetter A, Richards J, Costa DL (1998) Pulmonary responses to oil fly ash particles in the rat differ by virtue of their specific soluble metals. Toxicol Sci. 1998 43:204-12.
  14. Samet JM, Stonehuerner J, Reed W, Devlin RB, Dailey LA, Kennedy TP, Bromberg PA, Ghio AJ (1997) Disruption of protein tyrosine phosphate homeostasis in bronchial epithelial cells exposed to oil fly ash. Am J Physiol. 272:L426-32.
  15. Li XY, Gilmour PS, Donaldson K, MacNee W (1997) In vivo and in vitro proinflammatory effects of particulate air pollution (PM10). Environ Health Perspect 105 (S5):1279-83.
  16. Li XY, Gilmour PS, Donaldson K, MacNee W (1996) Free radical activity and pro-inflammatory effects of particulate air pollution (PM10) in vivo and in vitro. Thorax. 51:1216-22.
  17. Gilmour PS, Brown DM, Lindsay TG, Beswick PH, MacNee W, Donaldson K (1996) Adverse health effects of PM10 particles: involvement of iron in generation of hydroxyl radical. Occup Environ Med. 53:817-22.
  18. Donaldson K, Brown DM, Mitchell C, Dineva M, Beswick PH, Gilmour P, MacNee W (1997) Free radical activity of PM10: iron-mediated generation of hydroxyl radicals. Environ Health Perspect 105 (S5):1285-9.
  19. Becker S, Soukup JM, Gilmour MI, Devlin RB (1996) Stimulation of human and rat alveolar macrophages by urban air particulates: effects on oxidant radical generation and cytokine production. Toxicol Appl Pharmacol 141:637-48.
  20. Goldsmith CA, Frevert C, Imrich A, Sioutas C, Kobzik L (1997) Alveolar macrophage interaction with air pollution particulates. Environ Health Perspect. 105 (S5):1191-5.
  21. IARC Overall Evaluations of Carcinogenicity to Humans. International Agency for Research on Cancer, Lyons, France, 1999.

Relevant Wise Laboratory Publications

  1. Alley, D. F., Gordon, N. R., Langley-Turnbaugh, S., Wise, Sr., J.P., Van Epps, G. and Jalbert, A. The Effect of PM10 on Human Lung Fibroblasts. Toxicology and Industrial Health, 25: 111–120, 2009.

Collaborators and Cooperators

The Wise Laboratory is assisted in this work by an important number of collaborators and cooperators. In particular, the following prominent scientists and their teams provide significant support and input:

Dr. Lisa Pfefferle is Professor of Mechanical Engineering and the Chair of the Department of Chemical Engineering at Yale University. She provides expert advice and guidance on the creation and characterization of dusts and particles.

Dr. Douglas Thompson is a Professor of Epidemiology and Associate Director of the Maine Center for Toxicology and Environmental Health at the University of Southern Maine. He provides expert advice and guidance on statistical analysis and study design and also assists with the marine mammal studies.

Dr. Tongzhang Zheng is Professor of Epidemiology and Public Health and Head of the Environmental Health Sciences Division at Yale University. He provides expert advice and guidance on the statistical analysis and epidemiological design of marine mammal studies.

Funding

This work is generously supported by grant #EP-09-05 from the National Aeronautics and Space Administration (NASA) and by the Maine Center for Toxicology and Environmental Health.