In Vitro Cardiotoxicity of Residual Oil Fly Ash.

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Title: In Vitro Cardiotoxicity of Residual Oil Fly Ash.
Author: Knuckles, Travis
Advisors: Kenneth Adler, Committee Chair
Philip Sannes, Committee Member
Damian Shea, Committee Member
Kevin Dreher, Committee Member
Abstract: Epidemiological studies have shown an association between air pollution particulate matter (PM) and adverse cardiovascular effects. Although numerous mechanisms have been proposed, the actual mechanism(s) as well as emission sources and associated causal properties by which PM affects the cardiovascular system remain elusive. At least some adverse PM health effects can be attributed to bioavailable constituents, most notably, the transition metal content of the particles. Toxicological studies in rats using residual oil fly ash (ROFA) combustion source particles show extrapulmonary effects ranging from thermo-regulatory alterations, myocardial necrotic lesions, to fatal cardiac arrhythmias. Exposure of rats to ROFA via intratracheal instillation shows a rapid and transient increase in plasma metal content as early as 15mins post-exposure, suggesting that PM constituents are bioavailable to both the systemic circulation and perfused organs. However, the impact of this systemic exposure on extrapulmonary organs at the cellular and molecular levels is unknown. In this study, cardiomyocytes derived from 1-day-old rat pups were exposed to determine the direct effects of a particle free residual oil fly ash leachate (ROFA-L). Using concentration of leachate relevant to amount that were found in the plasma of rats following pulmonary deposition, I have shown that ROFA bioavailable constituents cytotoxicity in cardiomyocyte cultures and alter cardiomyocyte gene expression and transcription factor activation profiles consistent with alteration in cardiomyocyte growth and function.
Date: 2006-07-18
Degree: PhD
Discipline: Comparative Biomedical Sciences

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