Elucidation of the mechanism of gallium-arsenide induced pulmonary toxicity
AuthorRosner, Mitchell Harris
AdvisorCarter, Dean E.
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractGallium arsenide (GaAs) elicited a pulmonary inflammatory response in a dose dependent manner following a single exposure. A significant influx of leukocytes (polymorphonuclear cells) was observed 24 hours after intratracheal instillation of rats and hamsters. This led to an increase in the lung/body weight ratios. An increase in pulmonary DNA and total protein accompanied these observations. Histology confirmed the presence of increased numbers of pulmonary alveolar macrophages (PAM) even 1 week after exposure to GaAs. The instillation of GaAs also appeared to produce an oxidative stress in the lung only when the animals were given the 100 mg/kg dose and not the 10 mg/kg dose. Increased glutathione peroxidase and nonprotein sulfhydryls and depletion of ascorbic acid were evidence for the oxidative stress produced in the lung. These effects were dependent on the influx of phagocytic leukocytes. Analysis of the bronchoalveolar lavage fluid (BALF) also confirmed the involvement of phagocytic leukocytes in the progression of the lesions. Acid phosphatase activities increased significantly above the control levels 24 hours after exposure. The elevation of soluble protein and alkaline phosphatase indicated that the type I pneumocyte-capillary endothelial cell interface was compromised and the type II cells were damaged, respectively. The histological evaluations confirmed this phenomenon. Alveolar wall thickening was quite characteristic of the GaAs exposure. GaAs stimulated PAM to produce the active oxygen species, superoxide anion (O₂⁻) and H₂O₂, following in vitro and in vivo exposure. The dissolution of GaAs did not produce and O₂⁻ or H₂O₂ without the presence of cells. The cytotoxicity of GaAs was comparable to other compounds that elicit collagen deposition, As₂O₃ and silica. The semiconductor properties and potential dissolution products of GaAs may both contribute to its toxicity to PAM. The differences seen in the pulmonary lesions of silica (fibrosis) and GaAs (resorption of deposited collagen) treated animals may be due to the persistence of the particles. GaAs may be cleared by dissolution and silica cannot.
Degree ProgramPharmacology & Toxicology