Snyder A K, Singh S P, Ehmann S
Medical Research Service, Veterans Affairs Medical Center, Chicago, IL 60064.
Alcohol Clin Exp Res. 1992 Apr;16(2):295-300. doi: 10.1111/j.1530-0277.1992.tb01380.x.
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.
脑发育迟缓是胎儿酒精综合征（FAS）的主要特征。胰岛素和胰岛素样生长因子（IGF-I和IGF-II）对中枢神经系统（CNS）具有显著的促生长作用。本研究检测了乙醇及其与生长因子的相互作用对从足月胎鼠制备的原代星形胶质细胞培养物中标记前体掺入DNA、RNA和蛋白质的影响。在测量核苷或氨基酸掺入酸沉淀细胞成分之前，将培养物在无血清培养基中暴露于乙醇18小时。在基础条件下，乙醇诱导了氚标记胸腺嘧啶核苷、尿苷和缬氨酸掺入率的剂量依赖性变化。在100和200 mM乙醇存在下，掺入DNA的总胸腺嘧啶核苷摄取分数降低。对尿苷和缬氨酸掺入的影响与细胞摄取平行。胰岛素（10^(-6) M）和IGF-I（10^(-9) M）增加（p < 0.01）放射性标记胸腺嘧啶核苷、尿苷和缬氨酸的掺入。方差分析表明，乙醇与生长因子对核苷和缬氨酸掺入的影响之间存在高度显著的相互作用。干扰神经营养因子的作用可能是与母体摄入乙醇相关的胎儿脑发育迟缓的一个重要因素。
