Dissertation/Thesis Abstract

Effect of Particle Size and Composition on Silicate Toxicity in vitro and in vivo
by Blum, Alissa Claire, Ph.D., University of California, Davis, 2014, 91; 3637796
Abstract (Summary)

Exposure to air pollution particulates continues to be an important cause of respiratory and cardiovascular morbidity and mortality in people. Much research has examined the effects of polycyclic aromatic hydrocarbons, bacterial components, transition metals, salts and carbonaceous debris, though the mechanisms of nanoparticle transport from lung to systemic circulation remain uncertain. Particles of defined size and composition were used to compare the effects of size on mechanisms of transport and toxicity on barrier cells in the lung. Inert silica particles in the ultra-fine (UFP) range were found to enter human aortic endothelial or human pulmonary microvascular endothelial cells via caveolar-vesicular transport and to exert toxic effects within the cell by inducing generation of reactive oxygen species. Particles in the fine (FP) range were not able to enter cells and did not cause cellular dysfunction.

Silicosis is an inflammatory lung disease that affects both people and animals. Silica associated osteoporosis (SAO) is a chronic, degenerative skeletal disease of horses that is coincident with pulmonary silicosis induced by cristobalite. This study was undertaken to determine whether SAO was inducible in mice with intratracheal (IT) exposure to cristobalite crystals isolated from a horse with SAO. C57BL/6 (B6) and DBA/2 (D2) mice were treated with IT cristobalite and sacrificed after 16 weeks. Pulmonary silicosis was successfully induced in both strains of mice, but lesion composition was different between the strains. To determine if the treated mice were showing evidence of bone resportion, serum was analyzed via ELISA for markers of inflammation and bone resorption. D2 mice treated with cristobalite had increased serum concentrations of markers of inflammation and bone resportion relative to B6 cristobalite treated or control mice. No differences in number of lumbar vertebral osteoclasts were found between strains or treatment groups. . We conclude that environmental cristobalite induces strain specific pulmonary inflammation in mice that is associated with strain specific differences in serum markers of bone resportion.

Indexing (document details)
Advisor: Wilson, Dennis W.
Commitee: O'Donnell, Martha E., Tablin, Fern
School: University of California, Davis
Department: Molecular, Cellular and Integrative Physiology
School Location: United States -- California
Source: DAI-B 76/02(E), Dissertation Abstracts International
Subjects: Toxicology, Surgery, Pathology, Physiology
Keywords: Fine particulates, Mice, Nanoparticulates, Silica, Silica-associated osteoporosis, Ultrafine particulates
Publication Number: 3637796
ISBN: 978-1-321-21075-0
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