Teratogenic effects of ethanol during hyperplastic growth in cardiac myocyte cultures.
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.
Adickes
E D
ED
Department of Pathology, Creighton University School of Medicine, Omaha, Nebraska 68178.
Mollner
T J
TJ
Makoid
M C
MC
D000818:Animals; D000831:Animals, Newborn; D002310:Cardiomyopathy, Alcoholic / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology*; D008297:Male; D009206:Myocardium / Q000473:pathology; D011247:Pregnancy; D014176:Protein Biosynthesis; D051381:Rats
D000431:Ethanol; D004247:DNA