Weston W M, Greene R M, Uberti M, Pisano M M
Department of Anatomy and Developmental Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Alcohol Clin Exp Res. 1994 Feb;18(1):177-82. doi: 10.1111/j.1530-0277.1994.tb00900.x.
Fetal alcohol syndrome (FAS), which is brought about by maternal consumption of ethanol during pregnancy, is a major public health problem. To gain understanding of the etiology of this condition, a number of teratological studies have been performed in different animal systems to develop an animal model for FAS. The C57BL/6J mouse strain has been described as susceptible to the teratogenic effects of ethanol, whereas the ICR (CD-1) strain is considered relatively insensitive. We have compared the effects of ethanol on DNA and protein synthesis in cultured embryonic palate mesenchymal cells from both strains to determine if the reported differential sensitivity to ethanol is reflected in differences in ethanol's effects on cell behavior. Chronic exposure to 200 mM ethanol for 48 hr had a strong inhibitory effect on DNA synthesis in palate cells derived from both the C57BL/6J and ICR strains and a significant effect on protein synthesis in C57BL/6J palate cells. When we attempted to verify strain differences in susceptibility to ethanol teratogenesis, we were not able to observe an increased incidence of birth defects due to ethanol in either strain. High doses of ethanol (5.8 g/kg, administered by intraperitoneal injection on gestational day 8) resulted in death in both C57BL/6J and ICR mice. A lower dose (4.8 g/kg) caused decreased fetal weight and increased resorption in both strains, but did not bring about FAS-like craniofacial dysmorphology in either strain. It appears, therefore, that whereas ethanol can significantly affect the behavior of cells derived from craniofacial tissue, these effects cannot be correlated with sensitivity to ethanol teratogenesis in the mouse system.
胎儿酒精综合征（FAS）是孕期母亲摄入乙醇所致，是一个重大的公共卫生问题。为了解该病症的病因，已在不同动物系统中开展了多项致畸学研究，以建立FAS动物模型。C57BL/6J小鼠品系已被描述为对乙醇的致畸作用敏感，而ICR（CD-1）品系则被认为相对不敏感。我们比较了乙醇对这两个品系培养的胚胎腭间充质细胞中DNA和蛋白质合成的影响，以确定所报道的对乙醇的不同敏感性是否体现在乙醇对细胞行为影响的差异上。慢性暴露于200 mM乙醇48小时对来自C57BL/6J和ICR品系的腭细胞中的DNA合成有强烈抑制作用，并对C57BL/6J腭细胞中的蛋白质合成有显著影响。当我们试图验证对乙醇致畸作用的易感性品系差异时，在任何一个品系中都未能观察到因乙醇导致的出生缺陷发生率增加。高剂量乙醇（5.8 g/kg，在妊娠第8天腹腔注射）导致C57BL/6J和ICR小鼠均死亡。较低剂量（4.8 g/kg）导致两个品系的胎儿体重下降和吸收率增加，但在任何一个品系中都未引起FAS样颅面畸形。因此，虽然乙醇可显著影响颅面组织来源细胞的行为，但这些影响与小鼠系统中对乙醇致畸作用的敏感性无关。
