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Oxidant Air Pollutants and Lung Cancer: An Animal Model
EPA Grant Number: R828112C060Subproject: this is subproject number 060 , 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: Oxidant Air Pollutants and Lung Cancer: An Animal Model
Investigators: Witschi, Hanspeter , Schuller, Hildegard M.
Current Investigators: Witschi, Hanspeter , Breider, Michael A. , Schuller, Hildegard M.
Institution: University of California - Davis , University of Tennessee - Knoxville
EPA Project Officer: Katz, Stacey
Project Period: January 1, 1993 through December 31, 1993
RFA: Health Effects Institute (1996)
Research Category: Public/Private Partnership Center , Nitrogen Dioxide and Nitric Oxide
Description:
Objective:Ozone and nitrogen dioxide are highly reactive oxidant gases that are derived from the combustion of fossil fuels and the atmospheric transformation of these combustion products. The U.S. Environmental Protection Agency sets National Ambient Air Quality Standards (NAAQS) for these and other pollutants largely on the basis of scientific data documenting their effects on lung structure, function, and response to infectious agents. A major unanswered question is whether or not exposure to oxidant air pollutants contributes to lung cancer.
Small cell lung cancer, a highly malignant form of cancer, represents 25% of human lung cancers. Small cell lung tumors are composed primarily of cells with neuroendocrine characteristics. In the past, it has been difficult to investigate the role of environmental factors in the pathogenesis of small cell lung cancer because of the lack of a suitable animal model. However, an animal model for neuroendocrine lung cancer appeared to have been developed when Drs. Schuller, Witschi, and colleagues reported that hamsters developed neuroendocrine cell tumors when they were treated with the chemical carcinogen, diethylnitrosamine (DEN), while inhaling 70% oxygen. The investigators proposed that exposure to high oxygen concentrations (hyperoxia) caused neuroendocrine cells to proliferate and that the dividing cells were susceptible to tumor induction by DEN. Because exposure to both ozone and nitrogen dioxide also causes proliferation of lung cells, including neuroendocrine cells, the researchers suggested that these pollutants could mimic the effects of high oxygen exposures in tumor development. The Health Effects Institute sponsored the present study to examine whether exposure to ozone or nitrogen dioxide enhances the development of tumors induced by DEN, particularly neuroendocrine tumors, in the respiratory tract of hamsters.
Approach:Dr. Witschi exposed hamsters continuously to 0.8 ppm ozone for 16 weeks, or 15 ppm nitrogen dioxide for 16 or 24 weeks, or filtered air. The concentrations of the oxidant gases were much higher than those found in ambient air. However, the objective of the study was to determine whether the pollutants had any effects on lung tumor development under extreme conditions before testing ambient levels. Animals also received injections of DEN or saline twice each week. Hamsters exposed to 65% oxygen and injected with DEN were to serve as positive controls. Animals were killed after 16, 24, or 32 weeks, and various tissues were examined by the pathologists, Drs. Schuller and Breider, for neoplastic lesions (carcinomas, adenomas, papillary polyps) and nonneoplastic lesions (hyperplasia and necrosis). Supplemental Keywords:
Air, ambient air quality, air toxics, epidemiology, animal model, health effects, respiratory infection, combustion byproducts, particulate matter, nitrogen dioxide, ozone, disease. , Air, Scientific Discipline, Health, RFA, Toxicology, Risk Assessments, Health Risk Assessment, air toxics, Biochemistry, particulate matter, Environmental Chemistry, cancer risk, mobile sources, cancer risk assessment, Nitrogen dioxide, exposure and effects, ambient air quality, inhalation, lung cancer, carcinogens, ozone, environmental health effects, automobiles, emissions, human health risk, lung inflammation, lung injury, air pollutants, engines, human health effects, particulates, motor vehicles, ambient particle health effects, air pollution, environmental toxicants, inhalability, inhaled, lung, nitrogen, human health, lung epithelial cells, human exposure, animal model
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