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Mechanism of Oxidative Stress from Low Levels of Carbon Monoxide
EPA Grant Number: R828112C080Subproject: this is subproject number 080 , established and managed by the Center Director under grant R828112
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Health Effects Institute
Center Director: Greenbaum, Daniel S.
Title: Mechanism of Oxidative Stress from Low Levels of Carbon Monoxide
Investigators: Thom, Stephen R. , Ischiropoulos, Harry
Institution: University of Pennsylvania Medical Center, Philadelphia, , University of Pennsylvania Medical Center, Philadelphia, PA
Current Institution: University of Pennsylvania Medical Center, Philadelphia, PA
EPA Project Officer: Katz, Stacey
Project Period: April 1, 2000 through March 31, 2005
RFA: Health Effects Institute (1996)
Research Category: Carbon Monoxide , Public/Private Partnership Center
Description:
Objective:Carbon monoxide, an indoor and outdoor air pollutant, is produced by the incomplete combustion of fossil fuels. People are exposed to carbon monoxide from sources such as automobile emissions, industrial processes, sidestream or mainstream cigarette smoke, and poorly vented space heaters and gas stoves. Exposure to high levels of carbon monoxide (500 parts per million [ppm]) can lead to respiratory failure and death. Even low-level exposures can cause adverse health effects (for example, chest pain) in some people with coronary artery disease when they exercise. For this reason, the U.S. Environmental Protection Agency has set National Ambient Air Quality Standards for carbon monoxide of 9 ppm averaged over eight hours and 35 ppm averaged over one hour.
Some researchers speculate that exposure to carbon monoxide may be related to the development of atherosclerosis, a progressive disease characterized by deposits of fat, cholesterol, cells, and connective tissue in blood vessels. These deposits, called plaques, can block blood flow. That carbon monoxide may have a role in atherosclerosis is a public health concern because this disease is the leading contributor to deaths by heart attack and stroke in the United States.
One possible mechanism by which carbon monoxide might influence the development of atherosclerotic plaques involves nitric oxide, a gas once regarded primarily as an air pollutant from combustion sources. However, we now know that nitric oxide is also produced in the body. It is involved in regulating many physiological reactions, including those in the cardiovascular, immune, and nervous systems. Nitric oxide also can be converted to toxic metabolites such as peroxynitrite, which converts cholesterol-carrying low-density lipoproteins to a form that contributes to atherosclerotic plaque formation. An earlier study by Dr. Stephen Thom and coworkers demonstrated that blood platelets isolated from rats exposed to high levels of carbon monoxide (1,000 or 3,000 ppm) released nitric oxide. This finding suggested a possible link between carbon monoxide exposure, peroxynitrite formation from nitric oxide, and atherosclerosis. The Health Effects Institute funded this pilot study to examine the effects of low concentrations of carbon monoxide on platelets and cells isolated from blood vessels.
Approach:Thom and Ischiropoulos exposed blood platelets (taken from rats) and endothelial cells (isolated from bovine blood vessels) to varying concentrations of carbon monoxide and measured how much nitric oxide was released. To determine if exposure to carbon monoxide causes endothelial cells to produce peroxynitrite, the investigators looked for markers of its presence in the culture medium and in the cells. They also exposed rats to carbon monoxide by inhalation, isolated platelets from the rats' blood, and measured how much nitric oxide was released.
Supplemental Keywords:Air, ambient air quality, indoor air quality, air toxics, mobile sources, epidemiology, human health risk assessment, health effects, human exposure, second hand smoke, carbon monoxide. , Air, Scientific Discipline, Health, RFA, indoor air, Risk Assessments, Health Risk Assessment, air toxics, Biochemistry, particulate matter, Environmental Chemistry, mobile sources, cigarette smaoke, exposure and effects, ambient air quality, cardiovascular disease, coronary artery disease, environmental tobacco smoke, indoor air quality, inhalation, inhalation toxicology, air quality, ambient air, indoor exposure, second hand smoke, cigarette smoke, environmental health effects, automobiles, carbon monoxide, emissions, human health risk, lung inflammation, lung injury, air pollutants, engines, human health effects, particulates, motor vehicles, ambient particle health effects, air pollution, cardiac arrhythmias, inhalability, inhaled, lung, human health, human exposure
Progress and Final Reports:
Final Report
Main Center Abstract and Reports:
R828112 Health Effects Institute
Subprojects under this Center:
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R828112C042 Does Inhalation of Methanol Vapor Affect Human Neurobehavior?
R828112C043 Human Responses to Nitrogen Dioxide
R828112C044 The Role of Inflammation in Ozone-Induced Lung Injury
R828112C045 How Does Exercise Affect the Dose of Inhaled Air Pollutants?
R828112C046 How Do Chemicals in Diesel Engine Exhaust Damage DNA?
R828112C047 Effect of Nitrogen Dioxide on Bacterial Respiratory infection
in Mice
R828112C048 Effects of Ozone Exposure on Airway Epithelium
R828112C049 Inhalation of Aldehydes and Effects on Breathing
R828112C050 Does Ozone Cause Precancerous Changes in Cells?
R828112C051 Effects of Formaldehyde on Human Airway Epithelial Cells Exposed in a Novel Culture System
R828112C052 Carbon Monoxide and Cardiac Arrhythmias
R828112C053 Effects of Formaldehyde and Particle-Bound Formaldehyde on Lung Macrophage Functions
R828112C054 Mechanisms for Protecting Lung Epithelial Cells Against Oxidant Injury
R828112C055 Relationship of Nitropyrene-Derived DNA Adducts to Carcinogenesis
R828112C056 Particle Trap Effects on Heavy-Duty Diesel Engine Emissions
R828112C057 Carbon Monoxide and Atherosclerosis
R828112C058 Nitrogen Dioxide and Respiratory Illness in Children
R828112C059 Noninvasive Methods for Measuring Ventilation in Mobile Subjects
R828112C060 Oxidant Air Pollutants and Lung Cancer: An Animal Model
R828112C061 Detection of Carcinogen-DNA Adducts: Development of New Methods
R828112C062 Effects of Carbon Monoxide on Heart Muscle Cells
R828112C063 Development of Personal Ozone Samplers: Three Approaches
R828112C064 Development of Biomarkers to Monitor Carcinogen Exposure
R828112C065 Effects of Prolonged Ozone Inhalation on Collagen Structure and Content in Rat Lungs
R828112C065II Prolonged Ozone Exposure and the Contractile Properties of Isolated Rat Airways
R828112C065III Changes in Complex Carbohydrate Content and Structure in Rat Lungs Caused by Prolonged Ozone Inhalation
R828112C065IV Genetic Control of Connective Tissue Protein Synthesis After Prolonged Ozone Inhalation
R828112C065V Pulmonary Function Alterations in Rats After Chronic Ozone Inhalation
R828112C065VII Prolonged Ozone Exposure Leads to Functional and Structural Changes in the Rat Nose
R828112C065VIII - IX Studies of Changes in Lung Structure and Enzyme Activities
in Rats After Prolonged Exposure to Ozone
R828112C065X An Innovative Approach to Analyzing Multiple Experimental Outcomes: A Case Study of Rats Exposed to Ozone
R828112C065XI The Consequences of Prolonged Inhalation of Ozone on Rats:
An Integrative Summary of the Results of Eight Collaborative Studies
R828112C066 Interactive Effects of Nitropyrenes in Diesel Exhaust
R828112C067 Detection of Formaldehyde–DNA Adducts: Development of New Methods
R828112C068I Comparison of the Carcinogenicity of Diesel Exhaust and Carbon Black in Rat Lungs
R828112C068II An Investigation of DNA Damage in the Lungs of Rats Exposed to Diesel Exhaust
R828112C068III No Evidence For Genetic Mutations Found In Lung Tumors From Rats Exposed To Diesel Exhaust or Carbon Black
R828112C069 Noninvasive Determination of Respiratory Ozone Absorption: The Bolus-Response Method
R828112C070 The Effects of Inhaled Oxidants and Acid Aerosols on Pulmonary Function
R828112C071 Biochemical Consequences of Ozone Reacting with Membrane Fatty Acids
R828112C072 DNA Mutations in Rats Treated with a Carcinogen Present in Diesel Exhaust
R828112C073 Developmental Neurotoxicity of Inhaled Methanol in Rats
R828112C074 Methanol Distribution in Non Pregnant and Pregnant Rodents
R828112C075 Is Increased Mortality Associated with Ozone Exposure in Mexico City?
R828112C076 Effects of Fuel Modification and Emission Control Devices on Heavy-Duty Diesel Engine Emissions
R828112C077 Metabolic Studies in Monkeys Exposed to Methanol Vapors
R828112C078 Effects of Ozone on Pulmonary Function and Airway Inflammation in Normal and Potentially Sensitive Human Subjects
R828112C079 Improvement of a Respiratory Ozone Analyzer
R828112C080 Mechanism of Oxidative Stress from Low Levels of Carbon Monoxide
R828112C081 Long-Term Exposure to Ozone: Development of Methods to Estimate Past Exposures and Health Outcomes
R828112C082 Effects of Ambient Ozone on Healthy, Wheezy, and Asthmatic Children
R828112C083 Daily Changes in Oxygen Saturation and Pulse Rate Associated with Particulate Air Pollution and Barometric Pressure
R828112C084 Evaluation of The Potential Health Effects of the Atmospheric Reaction Products of Polycyclic Aromatic Hydrocarbons
R828112C085 Mechanisms of Response to Ozone Exposure: The Role of Mast Cells in Mice
R828112C086 Statistical Methods for Epidemiologic Studies of the Health Effects of Air Pollution
R828112C087 Development of New Methods to Measure Benzene Biomarkers
R828112C088 Alveolar Changes in Rat Lungs After Long-Term Exposure to Nitric Oxide
R828112C089 Effects of Prenatal Exposure to Inhaled Methanol on Nonhuman Primates and Their Infant Offspring
R828112C090 A Pilot Study of Potential Biomarkers of Ozone Exposure
R828112C091 Effects of Concentrated Ambient Particles on the Cardiac and Pulmonary Systems of Dogs
R828112C092 Cancer, Mutations, and Adducts in Rats and Mice Exposed to Butadiene and Its Metabolites
R828112C093 Effects of Concentrated Ambient Particles in Rats and Hamsters: An Exploratory Study
R828112C094I The National Morbidity, Mortality, and Air Pollution Study: Methods and Methodologic Issues
R828112C094II The National Morbidity, Mortality, and Air Pollution Study: Morbidity and Mortality from Air Pollution in the United States
R828112C095 Association of Particulate Matter Components with Daily Mortality and Morbidity in Urban Populations
R828112C096 Acute Pulmonary Effects of Ultrafine Particles in Rats and Mice
R828112C097 Identifying Subgroups of the General Population That May Be Susceptible to Short-Term Increases in Particulate Air Pollution
R828112C098 Daily Mortality and Fine and Ultrafine Particles in Erfurt, Germany
R828112C099 A Case-Crossover Analysis of Fine Particulate Matter Air Pollution and Out-of-Hospital Sudden Cardiac Arrest
R828112C100 Effects of Mexico City Air on Rat Nose
R828112C101 Penetration of Lung Lining and Clearance of Particles Containing Benzo[a]pyrene
R828112C102 Metabolism of Ether Oxygenates Added to Gasoline
R828112C103 Characterization and Mechanisms of Chromosomal Alterations Induced by Benzene in Mice and Humans
R828112C104 Acute Cardiovascular Effects in Rats from Exposure to Urban Ambient Particles
R828112C105 Genetic Differences in Induction of Acute Lung Injury and Inflammation in Mice
R828112C106 Effects on Mice of Exposure to Ozone and Ambient Particle Pollution
R828112C107 Emissions from Diesel and Gasoline Engines Measured in Highway Tunnels