title: Interactive effects of ethanol and caffeine on rat fetal hepatocyte replication and EGF receptor expression.
abstract: This study reports on the interactive effects of ethanol and caffeine on growth of rat fetal hepatocytes. Exposure of cultured rat fetal hepatocytes (RFH) to ethanol in concentrations above 1 mg/ml, causes a blockade of EGF-dependent cell replication along with an overexpression of surface EGF receptors (EGF-R). However, RFHs exposed for 24 hours to ethanol at a concentration of 1 mg/ml alone had little effect on cell replication. Caffeine, when combined with this concentration of alcohol, progressively impaired RFH growth by up to 100%. Caffeine alone up to 10 micrograms/ml, on the other hand, caused a progressive increase in RFH replication associated with a 69% enhancement of DNA synthesis. Caffeine concentrations in excess of 50 micrograms/ml had no effect on replicative capacity. Concomitant caffeine exposure had no effect on the ethanol-related increase in cell DNA content, yet it caused a further enhancement of the cell protein accural induced by ethanol alone. Caffeine (10 micrograms/ml) alone had no effect on EGF-R expression, while ethanol (2 mg/ml) increased it by almost 200%. Addition of caffeine to ethanol reduced this enhanced EGF binding by 45%. Scatchard analysis indicated that no treatment altered ligand affinity for the receptor, but that the alterations in binding caused by ethanol and the caffeine/ethanol combination reflected changes in binding capacity, in both low and high affinity components. It is concluded that (1) ethanol blocks EGF-mediated replication accompanied by a reduction in DNA synthesis, (2) caffeine alone at low concentrations has the opposite effect and can actually potentiate the EGF-mediated mitogenic response, (3) caffeine in combination with ethanol acts synergistically to reduce RFH replication.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7878.
authors.forename: G I
authors.initials: GI
authors.lastname: Henderson
authors.forename: G S
authors.initials: GS
authors.lastname: Baskin
authors.forename: T A
authors.initials: TA
authors.lastname: Frosto
authors.forename: S
authors.initials: S
authors.lastname: Schenker
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D066246:ErbB Receptors / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005333:Fetus; D008099:Liver / Q000166:cytology*; D011247:Pregnancy; D051381:Rats
chemical_list: D002110:Caffeine; D000431:Ethanol; D066246:ErbB Receptors