Degree Granting Department
Raymond D. Harbison
Cytotoxicity, Ethanol Insensitivity, HepG2, Poly(ADP-Ribsoe) Polymerase
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.
Scholar Commons Citation
Coyle, Jayme, "The Assessment of an In-vitro Model for Evaluating the Role of PARP in Ethanol-mediated Hepatotoxicity" (2013). Graduate Theses and Dissertations.