This investigation assesses the role of poly(ADP-ribose) polymerase in ethanol-mediated hepatotoxicity using the untransfected HepG2 hepatocellular carcinoma line, an established, well-characterized toxicological model. HepG2 cells were treated with ethanol at concentrations between 100 mM and 800 mM, and assessed for markers of cytotoxicity. PARP-1 activity in total cell protein lysates was quantified as a proxy of apoptotic induction at six hours. Our results demonstrated a 1.43-fold AST activity increase in culture medium isolates of cells exposed to 800 mM without significant effect on cellular viability. PARP-1 activity varied greatly and results for enzyme activity remained inconclusive. The results suggest a high degree of insensitivity to ethanol toxicity and nuclear enzyme activity, demonstrating the metabolic irrelevance of untransfected HepG2 in ethanol toxicosis. There is a need to characterize phase 1 metabolic enzyme expression profiles relevant to ethanol for CYP2E1 and ADH pathways to facilitate comparisons across toxicological models using transfected, as well as the untransfected HepG2 model.
Identifer | oai:union.ndltd.org:USF/oai:scholarcommons.usf.edu:etd-6006 |
Date | 01 January 2013 |
Creators | Coyle, Jayme |
Publisher | Scholar Commons |
Source Sets | University of South Flordia |
Detected Language | English |
Type | text |
Format | application/pdf |
Source | Graduate Theses and Dissertations |
Rights | default |
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