Adickes E D, Mollner T J, Makoid M C
Department of Pathology, Creighton University School of Medicine, Omaha, Nebraska 68178.
Alcohol Clin Exp Res. 1993 Oct;17(5):988-92. doi: 10.1111/j.1530-0277.1993.tb05653.x.
Ethanol alters cellular growth and maturation, teratologic factors that are recognized as contributing to abnormal phenotypic expression. Cultured neonatal Sprague-Dawley rat cardiac myocytes were utilized to determine how ethanol alters growth and development. Two ethanol exposure paradigms were studied: (1) constant, to cultures in closed chambers for 7 days at low (10 mM) and high (50 mM) concentrations; and (2) periodic (24-hr) to cells during hyperplastic growth. In constantly exposed cultures, 10 and 50 mM ethanol concentrations depressed the rate of leucine incorporation and the rate of thymidine uptake during early hyperplastic growth (log phase growth). A resultant slower expansion of cell populations was noted. Although the period of maximum vulnerability appeared to be the hyperplastic growth phase, a second set of experiments using 10 and 50 mM ethanol were performed to assess the effects of short (24-hr) exposures. DNA synthesis was depressed during early hyperplastic growth compared with controls (days 2-4), reflected as a decrease in thymidine incorporation and smaller cell population. This study demonstrates that ethanol depresses both DNA and protein synthesis during hyperplastic growth resulting in an insufficient, protein-deficient cell mass, incapable of participating in normal embryogenesis.
乙醇会改变细胞的生长和成熟，这些致畸因素被认为是导致异常表型表达的原因。利用培养的新生Sprague-Dawley大鼠心肌细胞来确定乙醇如何改变生长和发育。研究了两种乙醇暴露模式：（1）持续暴露，在密闭培养箱中以低浓度（10 mM）和高浓度（50 mM）培养7天；（2）在细胞增生性生长期间进行周期性（24小时）暴露。在持续暴露的培养物中，10 mM和50 mM乙醇浓度在早期增生性生长（对数期生长）期间降低了亮氨酸掺入率和胸苷摄取率。结果发现细胞群体的扩张速度较慢。尽管最大易损期似乎是增生性生长阶段，但仍进行了另一组使用10 mM和50 mM乙醇的实验，以评估短期（24小时）暴露的影响。与对照组（第2 - 4天）相比，在早期增生性生长期间DNA合成受到抑制，表现为胸苷掺入减少和细胞群体变小。这项研究表明，乙醇在增生性生长期间会抑制DNA和蛋白质合成，导致细胞质量不足、蛋白质缺乏，无法参与正常的胚胎发生。
