Nanoparticle toxicity and oxidative stress assessed through pulmonary cell models

Abstract

Thesis (Ph. D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Environmental Medicine, 2007.Nanomaterials are defined by the National Nanotechnology Initiative as those materials with at least one dimension less than 100 nanometers and possessing unique characteristics due to their small size. These unique properties are responsible for the dramatic growth in their proposed utilization in a multitude of new applications. With their increase in use and production comes the potential for increased human exposure to materials with poorly characterized toxicological profiles. Inhalation has been identified as one of the major routes of exposure for nanoparticles both occupationally and environmentally. Detailed modeling and experimental data reveal that nanoparticles are capable of being deposited deep within the pulmonary system in the alveolar regions. Particulate matter has long been recognized as a risk factor associated with both morbidity and mortality. Hypotheses about the effects reveal that reactive oxygen species (ROS) may play a role in associated toxicities associated with nanoparticles. The ROS have been demonstrated as being generated from the particle itself as intrinsic activity, or by the cell, or both. The results presented here demonstrate that nanoparticles are capable of interacting with the cell and are taken up by active processes. The exposure of cells to nanoparticles resulted in an increase in ROS and subsequently alterations in antioxidant systems as well as cell death. The effects produced varied based on particle composition, duration of exposure, presence of a coating, and cell type used in the investigation. Results indicate that although size of nanoparticles makes them a unique class of materials, the chemical composition of the particle was the dominating factor in determining the impact the nanoparticle would have on the cells. Additionally it was observed that in evaluating nanoparticles several cell systems should be used since the particles act differently on the various cell lines. This research has provided a basis for future nanoparticle research and revealed how multi factorial the research is in nanotoxicology