Repeated inhalation exposure to particles can lead to chronic respiratory disease. One particle that has been identified as being especially toxic to the lung is asbestos. Asbestos was widely used in the United States throughout the 20th century. Due to it’s discovered toxic impacts, governmental controls have dramatically reduced the use of asbestos in the US during the last 40 years, and implemented safety measures to prevent high dose exposures. However, this is not the case in many developing countries where asbestos use is continuing to increase at a high rate. Disease development due to asbestos exposure varies depending on the individual. The risk for disease development depends on genetic and environmental factors. While genetic factors typically cannot be altered, environmental risk factors are often modifiable. Two of the modifiable risk factors for disease development, which contribute the most to increased health care costs are obesity and tobacco smoke exposure. Not only does tobacco smoke exposure appear to impact disease development for smokers, but also for non-smokers who are exposed to tobacco smoke in the environment; this is especially the case in children. This study explored the effects of the modifiable risk factors: obesity and environmental tobacco smoke, on disease development after asbestos exposure. While obesity appeared to increase acute inflammatory response to asbestos, the effect of obesity on chronic disease development after asbestos exposure was less clear. Environmental tobacco smoke appeared to suppress initial inflammatory response, which lead to an increase in disease development chronically. The last section of this study focuses on additional particles that have been identified as being potentially toxic to the lung: carbon nanotubes. Carbon nanotubes are similar in shape to asbestos fibers, although they differ in size and chemical composition. Manufacturing of carbon nanotubes started in the 1990s. However, their use has grown dramatically within the last decade as more applications for the materials are discovered. Given the increase in applications for carbon nanotubes, which coincides with increased risk of exposure, and evidence supporting their toxic potential, it is important to understand mechanisms behind carbon nanotube toxicity. Our study attempts to get a better understanding of the mechanisms of action behind carbon nanotube disease development as well as to identify biomarkers of exposure and subsequent disease development. Epigenetics is an emerging field that looks at non-coding changes to the DNA that can effect gene expression. Epigenetics has been shown to effect response to exposure and it has been used as a biomarker for disease development. In this study, we found both epigenetic indicators of disease development, and biomarkers of exposure.
|Commitee:||Cho, Yoon Hee, Coffin, Douglas, Migliaccio, Christopher, Sugden, Kent|
|School:||University of Montana|
|School Location:||United States -- Montana|
|Source:||DAI-B 77/03(E), Dissertation Abstracts International|
|Subjects:||Toxicology, Surgery, Nutrition, Immunology|
|Keywords:||Lifestyle effects, Particle, Toxicology|
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