An important effect of ethanol is to disrupt cellular growth. Specifically ethanol has been shown to inhibit hepatocyte DNA synthesis by a number of agents including epidermal growth factor (EGF) (Carter EA, Wands JR, Biochem Biophys Res Commun 1985;128:767:774). In an attempt to understand the mechanism by whcih ethanol interferes with the normal processes of growth and development we studied the early metabolite changes induced by EGF, platelet derived growth factor (PDGF) and angiotensin in rat liver in vivo (Reed BY, King MT, Gitomer WL, Veech RL, J Biol Chem 1987;262:8712- 8715; Reed BY, King Mt, Gerhart MJ, Veech RL, Biochem Soc Trans 1988;16:636-637). Elucidation of the metabolic changes induced enabled us to identify 2 enzymes affected by the actions of EGF and PDGF respectively. We have subsequently demonstrated a direct effect of ethanol on the normal metabolic action of EGF in vivo (Gehart MJ, Reed BY, Veech RL, Alcoholism: Clin and Exp Res 1988;12:116-118) and further shown that the apparent modulation of the action of EGF by ethanol occurs at an intracellular site as ethanol does not interfere with the binding of the growth factor to its receptor (Gerhart MJ. Reed BY, Veech RL, In: Advances in Alcohol and Substance Abuse. 1988; in press). Currently further studies are in progress to elucidate the role of PDGF in alcoholic liver disease.
