The Role of Environmental Nitrogen Oxide Species in the Induction of Cholesterol Accumulation in Vascular Cells
Principal Investigator(s): Liana Asatryan, Ph.D., post-doctoral student, Department of Molecular Pharmacology and Toxicology, USCDescription: The role of NOx species as environmental oxidants in the development of atherosclerosis has not been studied sufficiently. LDL oxidation is a crucial event in early atherogenesis and specific NOx species (i.e., NO) have been implicated in the disease etiology. The investigators have recently found a novel, hemoglobin-dependent mechanism for mildly oxidized LDL formation in whole blood. This LDL bears higher electronegative charge (LDL-) and has atherogenic properties. NOx are able to cause intravascular hemolysis and react avidly with hemoglobin. The aim of this project was to determine whether exposure to environmental NOx can lead to increased LDL- levels via hemolysis and if this modified LDL promotes cholesterol accumulation in vascular cells.
Award Amount: $16,000
Use of GIS to Characterize Air Toxics Hot Spots in the South Coast Air Basin
Principal Investigator(s): L. Donald Duke, Ph.D., PE, Principal Investigator and doctoral student Michelle Wilhelm, School of Public Health, UCLA
Description: This research uses Geographic Information System methods to investigate the distribution of air toxics sources and to identify populations that may be disproportionately exposed to emissions potentially harmful to health. The specific focus is the spatial distribution of diesel exhaust sources in the South Coast Air Basin. Both mobile sources (such as trucks and passenger vehicles) and stationary sources (such as delivery trucks idling for long periods at industrial facilities) will be investigated. Expected contributions from this pilot project include: (1) indication of the approximate contribution of mobile versus stationary sources to overall diesel emissions; (2) identification of communities potentially at risk from exposure to diesel exhaust and which may require localized air monitoring; and (3) identification of data gaps in regard to diesel emissions characterization in the South Coast Air Basin.
Award Amount: $16,000
Development of Respiratory Biomarkers in Sputum
Principal Investigator(s): Frank Gilliland, M.D., Ph.D., Department of Preventive Medicine, USC
Description: This pilot study investigates the use of biomarkers in sputum to study respiratory carcinogenesis in former smokers using a molecular epidemiology approach to these groups. The need for research is evident. Lung cancer remains a pressing worldwide public health problem. New techniques of molecular and cellular biology may also provide markers for studying the effects of air pollution as well as the longitudinal process of carcinogenesis, for screening, and for use in intervention trials. The long-range goals are to describe and validate markers for lung cancer and effects of air pollution, and to use these markers to further characterize the respiratory effects of air pollution and quantitative lung cancer risks after cessation of smoking. In this pilot project, methods will be developed and feasibility will be assessed for using biomarkers in exfoliated respiratory tract cells from sputum in molecular epidemiologic studies.
Award Amount: $16,000
Modification of Colorectal Cancer Risk Factors by MPO and NQO1 Genotype
Principal Investigator(s): Sue Ingles, Ph.D., USC/Norris Comprehensive Cancer Center
Description: This is a study to determine whether risk factors for colorectal cancer might be modified by polymorphisms in two genes that encode carcinogen-metabolizing enzymes. The NQO1 gene encodes the enzyme NAD(P)H:quinone oxidoreductase, an enzyme that catalyzes reductive activation of certain environmental carcinogens, including nitroaromatic compounds and heterocyclic amines. The second gene, MPO, encodes myeloperoxidase, which catalyzes the endogenous formation of free radicals and activates benzo[a]pyrene and aromatic amines. Both heterocyclic amine exposure and smoking are risk factors for colorectal cancer. Both of these risk factors have been found to be associated with risk of colorectal adenomas in an ongoing case-control study being conducted at two Kaiser Medical Centers in Los Angeles County. Using DNA that is available for these subjects, the investigators propose to genotype the MPO and NQO1 polymorphisms, and to re-examine the effects of smoking and heterocyclic amine exposure within genotypically defined strata.
Award Amount: $16,000
Respiratory Health and Air Pollution in Los Angeles and Mexico City
Principal Investigator(s): Rob McConnell, M.D., Department of Preventive Medicine, USC
Description: This pilot project will compare results from the Mexican and Los Angeles studies of children's respiratory health and chronic exposure to air pollution. The feasibility of merging data sets and the consistency of cross sectional results from the two countries will be determined. The studies have similar designs, in which lung function of children has been examined cross sectionally and is being followed longitudinally. The 2000 Mexican children are recruited from schools in 10 communities in Mexico City, some of which have exposures to ozone and PM-10 two or three times the U.S. standards. To the extent feasible, the same analytic models and variables will be used in this analysis as in the L.A. study to see if the associations between air pollution and lung function observed in L.A. are confirmed. Weak associations observed in L.A. will be evaluated in the context of the higher exposures to pollutants in Mexico.
Award Amount: $16,000