Elucidation of the mechanism of gallium-arsenide induced pulmonary toxicity.

Persistent Link:
http://hdl.handle.net/10150/184627
Title:
Elucidation of the mechanism of gallium-arsenide induced pulmonary toxicity.
Author:
Rosner, Mitchell Harris
Issue Date:
1989
Publisher:
The University of Arizona.
Rights:
Copyright © 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.
Abstract:
Gallium 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.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Gallium arsenide semiconductors -- Toxicology.; Pulmonary toxicology.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Pharmacology and Toxicology; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Carter, Dean E.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleElucidation of the mechanism of gallium-arsenide induced pulmonary toxicity.en_US
dc.creatorRosner, Mitchell Harrisen_US
dc.contributor.authorRosner, Mitchell Harrisen_US
dc.date.issued1989en_US
dc.publisherThe University of Arizona.en_US
dc.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.en_US
dc.description.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.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectGallium arsenide semiconductors -- Toxicology.en_US
dc.subjectPulmonary toxicology.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePharmacology and Toxicologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorCarter, Dean E.en_US
dc.contributor.committeememberSipes, I. Glennen_US
dc.contributor.committeememberMayersohn, Michaelen_US
dc.contributor.committeememberBrendel, Klausen_US
dc.contributor.committeememberAposhian, H. Vaskenen_US
dc.identifier.proquest8907970en_US
dc.identifier.oclc701925999en_US
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