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Effects of Formaldehyde on Human Airway Epithelial Cells Exposed in a Novel Culture System
EPA Grant Number: R828112C051Subproject: this is subproject number 051 , 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: Effects of Formaldehyde on Human Airway Epithelial Cells Exposed in a Novel Culture System
Investigators: Klein-Szanto, Andres J.P. , Bonfil, Daniel , Litwin, Samuel , Momiki, Shigeru , Ura, Hitoshi
Institution: Fox Chase Cancer Center, Philadelphia, PA
Current Institution: Fox Chase Cancer Center, Philadelphia, PA , City of Philadelphia, PA
EPA Project Officer: Katz, Stacey
Project Period:
RFA: Health Effects Institute (1996)
Research Category: Public/Private Partnership Center , Air Toxics
Description:
Objective:Whether or not the air pollutant formaldehyde is injurious to human health is controversial. Results from human epidemiological studies, animal inhalation studies, and cell culture assays suggest that formaldehyde has the potential to cause adverse human health effects, including cancer. Based on these findings, the 1990 Amendments to the Clean Air Act specifically define formaldehyde as a toxic air pollutant.
Motor vehicle emissions currently contain formaldehyde. An increased use of alcohols, particularly methanol, as alternative fuels and in fuel blends may increase outdoor levels of formaldehyde because their combustion yields greater formaldehyde emissions than conventional fuel combustion. Whether such emissions will increase the risk of cancer for humans is unknown.
Cells lining the airways (epithelial cells) are a frequent site of cancer origin in humans. This study, sponsored by the Health Effects Institute, employed a novel exposure system to explore the capacity of formaldehyde to cause cancerous changes in human epithelial cells. This exposure system provided special growth conditions for the cells withing a laboratory animal (in vivo) that closely mimicked the cells' usual environment in the human trachea.
Approach:Dr. Klein-Szanto and colleagues obtained autopsy samples from human infant airways and from adult nasal tissue. They propagated the epithelial cells in culture and injected them into isolated segments of rat tracheas from which the epithelium had been removed. The tracheas then were placed under the skin of mice to allow the cells to attach and grow in the tracheas. Unlike most other cell culture systems, this exposure system provided a support structure similar to that of the human trachea, as well as many substances important for cell growth. Another advantage was that cells from one tissue sample were propagated and used for many experiments; this reduced the variability caused by using cells from different samples for different experiments. For the exposures, the investigators inserted into the tracheas small silicon tubes containing different amounts of powdered formaldehyde. After 2, 4, 8, and 16 weeks, they evaluated the epithelial cells' appearance and determined the formaldehyde dose that produced the most cell changes. They also exposed the cells to formaldehyde alone and in combination with a potent carcinogen (a metabolite of benzo[a]pyrene) for 6 to 12 months and looked for cell changes suggesting cancer. Supplemental Keywords:
Air, ambient air quality, air toxics, epidemiology, health effects, inhalation studies, particulate matter, human exposure, human health risk assessment, susceptibilty, formaldehyde, mobile sources, alternative fuels. , Air, Scientific Discipline, Health, RFA, Toxicology, Risk Assessments, Health Risk Assessment, air toxics, Biochemistry, particulate matter, Environmental Chemistry, cancer risk, mobile sources, automotive, automotive exhaust, cancer risk assessment, Formaldehyde, carcinogen, exposure and effects, engine exhaust, ozone carcinogen, ambient air quality, inhalation, inhalation toxicology, methanol vapor, carcinogens, ozone, aerosol particles, DNA adducts, environmental health effects, emissions, human health risk, lung inflammation, lung injury, air pollutants, human health effects, particulates, neurotoxic, ambient particle health effects, cancer causation, air pollution, environmental toxicants, inhalability, inhaled, lung, automotive emissions, epithelial cells, human health, human exposure, neurotoxicity
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