Document Detail

Basic fibroblast growth factor- and platelet-derived growth factor-mediated cell proliferation in B104 neuroblastoma cells: effect of ethanol on cell cycle kinetics.
MedLine Citation:
PMID:  9372213     Owner:  NLM     Status:  MEDLINE    
In vivo studies show (a) that early exposure to ethanol depletes neurons in the central nervous system (CNS) and (b) that a primary target of ethanol in the developing nervous system is proliferating neuronal precursors. We used a neuronal cell line (B 104 neuroblastoma cells) as an in vitro model for the effects of ethanol on the proliferation of neuronal precursors to test the hypothesis that ethanol interferes with growth factor-regulated proliferation of neuron-like precursors. The effects of ethanol on the mitogenic activity of two growth factors, basic fibroblast growth factor (bFGF) and platelet-derived growth factor AA and BB (PDGF-AA and PDGF-BB), were examined. Cell proliferation was monitored by tracing the change in the numbers of cultured cells over 4-5 days and in the cell cycle kinetics was determined using a cumulative labeling technique with bromodeoxyuridine (BrdU). Western immunoblots and immunohistochemical preparations show that B104 cells expressed the high affinity receptors for bFGF, PDGF-AA and PDGF-BB. The three growth factors were potent mitogens for the B104 cells; they promoted an increase in cell number even when the cells were grown in serum-free medium. Ethanol depressed the bFGF-, PDGF-AA- and PDGF-BB-mediated cell proliferation without altering the incidence of cell death. These changes in proliferation were concentration-dependent; at a concentration of 100 mg/dl, ethanol partially, but significantly inhibited growth factor-stimulated proliferation and higher ethanol concentrations (400 mg/dl or more) completely abolished growth factor-regulated cell proliferation. The effects of ethanol on cell growth were a result of ethanol-induced changes in growth factor-regulated cell cycle kinetics, principally the total length of the cell cycle and the fraction of the population that was actively cycling (the growth fraction). Ethanol completely negated the action of bFGF, but only partially blocked PDGF-promoted cycling activity. Thus, B104 cells are a suitable model for studying the effects of ethanol on neuronal proliferation. The blockage of bFGF- and PDGF-mediated cell proliferation by ethanol supports the hypothesis that growth factors are a target of ethanol neurotoxicity. Furthermore, the differential actions and effects of ethanol on the two growth factors mirror effects observed in vivo.
J Luo; M W Miller
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Brain research     Volume:  770     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  1997 Oct 
Date Detail:
Created Date:  1998-01-21     Completed Date:  1998-01-21     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  139-50     Citation Subset:  IM    
Department of Psychiatry-M.E.B., University of Iowa College of Medicine, Iowa City 52242-1000, USA.
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MeSH Terms
Anticoagulants / pharmacology*
Blood Proteins / pharmacology
Cell Cycle / drug effects
Central Nervous System Depressants / pharmacology*
Culture Media, Serum-Free / pharmacology
Ethanol / pharmacology*
Fibroblast Growth Factor 2 / pharmacology*
Platelet-Derived Growth Factor / pharmacology*
Receptors, Growth Factor / analysis,  biosynthesis,  metabolism
S Phase / drug effects
Tumor Cells, Cultured / chemistry,  cytology,  drug effects
Grant Support
Reg. No./Substance:
0/Anticoagulants; 0/Blood Proteins; 0/Central Nervous System Depressants; 0/Culture Media, Serum-Free; 0/Platelet-Derived Growth Factor; 0/Receptors, Growth Factor; 0/platelet-derived growth factor A; 0/platelet-derived growth factor BB; 103107-01-3/Fibroblast Growth Factor 2; 64-17-5/Ethanol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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