Ambient Particulate Matter
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.
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.
|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|
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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.
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.