Effects of ethanol on DNA, RNA, and protein synthesis in rat astrocyte cultures.
Brain growth retardation is a major feature of the fetal alcohol syndrome (FAS). Insulin and insulin-like growth factors (IGF-I and IGF-II) exert significant growth-promoting effects on the central nervous system (CNS). The present study examined the effects of ethanol and its interactions with growth factors on the incorporation of labeled precursors into DNA, RNA, and protein in primary astrocyte cultures prepared from term fetal rats. Cultures were exposed to ethanol for 18hr in serum-free medium before measuring nucleoside or amino acid incorporation into acid-precipitable cell constituents. Under basal conditions, ethanol induced dose-dependent changes in the rates of incorporation of tritiated thymidine, uridine, and valine. The fraction of the total thymidine uptake that was incorporated into DNA was reduced in the presence of 100 and 200 mM ethanol. Effects on uridine and valine incorporation paralleled cell uptake. Insulin (10(-6) M) and IGF-I (10(-9) M) increased (p less than 0.01) incorporation of radiolabeled thymidine, uridine, and valine. Analysis of variance indicated highly significant interactions between ethanol and the effects of growth factors on incorporation of both nucleosides and valine. Interference with the action of neurotrophic factors may be a significant factor in fetal brain growth retardation associated with maternal ethanol ingestion.
Snyder
A K
AK
Medical Research Service, Veterans Affairs Medical Center, Chicago, IL 60064.
Singh
S P
SP
Ehmann
S
S
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D012313:RNA / Q000096:biosynthesis*; D051381:Rats; D013936:Thymidine / Q000378:metabolism; D014529:Uridine / Q000378:metabolism; D014633:Valine / Q000378:metabolism
D007328:Insulin; D009419:Nerve Tissue Proteins; D000431:Ethanol; D012313:RNA; D007334:Insulin-Like Growth Factor I; D004247:DNA; D014633:Valine; D013936:Thymidine; D014529:Uridine