Effects of diesel soot, residual oil fly ash, and carbon black particles in rat lung tissue slice cultures and A549 cell cultures
Abstract
The purpose of this thesis was to investigate the effects of particles in two in vitro bioassay systems, namely, rat lung slice cultures and human A549 cells. The goals were to determine (1) if the treatment of these systems with particles would produce different intensities of responses, and (2) if these differences would be predictive of the relative risk associated with the inhalation of the particles. Rat lung slice cultured for 11 days with harvests on day 0, 1, 4, 7, and 11. In control slices, transient increases in tumor necrosis factor-α (TNF-α) and macrophage inflammatory protein-2 (MIP-2) secretion on day 1 and in protein synthesis and alveolar type II pneumocytes on day 4 were thought to reflect a wound repair mechanism. That process appeared to be complete by day 7, at which time homeostasis was achieved. The treatment of the lung slices with 1 mg/ml of residual oil fly ash (ROFA), diesel soot (DS), or carbon black (CB) altered adenosine triphosphate (ATP) content, protein synthesis, and MIP-2 release that indicated a relative toxicity of ROFA > DS > CB = vehicle controls. Viability was maintained in control slices for the complete 11-day culture duration. A549 cells were treated with 40 μg/cm2 of these particles, and additionally, nickel subsulfide (Ni3S2), crystalline silica (Si), titanium dioxide (TiO2). or an ambient air particulate sample from Ottawa, Canada (OAA). Alterations in ATP content, lactate dehydrogenase release, protein synthesis, and interleukin-8 and growth-regulated oncogene-alpha release indicated a relative toxicity Of Ni3S2 > ROFA > Si, OAA, DS, CB, TiO2. Although the toxicity signatures in these two in vitro assays were consistent with mechanism-based assessments of toxicity in vivo, the assays showed much variability and little sensitivity for differentiating similar particles of low in vivo toxicity.
Degree
Ph.D.
Advisors
Rebar, Purdue University.
Subject Area
Toxicology
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