title: Differential sensitivity of mouse neural crest cells to ethanol-induced toxicity.
abstract: Neural crest cells (NCCs) have been identified as an important target population relative to ethanol-induced teratogenicity in both mouse and avian models. Additionally, whole embryo culture mouse models have shown strain-related differences in sensitivity to ethanol-induced damage following acute exposure during early NCC development. That differential sensitivity of NCCs may contribute to these strain differences has been unexplored. For this purpose, cultured NCCs from an inbred mouse strain (C57BL/6J; C57) that is more sensitive to ethanol-induced teratogenicity than an outbred strain (ICR) were compared. This study showed that the incidence of cell death was significantly higher for the C57 NCCs than those from the ICR strain at all ethanol concentrations tested, and as early as 12 hours after initial exposure to 100 mM ethanol. The lateral mobility of the membrane lipids was faster and the membrane GM1 content was lower in C57 cells than ICR cells both under control conditions and at all doses and times tested. Ethanol exposure resulted in significant increases in the membrane lipid lateral mobility, and decreases in the membrane GM1 content that occurred in a dose and time-dependent manner in the NCCs from both strains. A significant correlation was found between the GM1 content and lateral mobility of the membrane lipids, the lateral mobility of membrane lipids and cell viability, as well as the GM1 content and cell viability in the NCCs from both strains. These results suggest that different strain sensitivities to ethanol-induced teratogencity may lie, at least in part, in the interstrain differential response of the NCC population and that the vulnerability of the NCCs to ethanol-induced death may be related to their endogenous membrane GM1 content.
authors.affiliation: Department of Cell Biology and Anatomy, University of North Carolina at Chapel Hill, 27599-7090, USA.
authors.forename: S Y
authors.initials: SY
authors.lastname: Chen
authors.forename: A
authors.initials: A
authors.lastname: Periasamy
authors.forename: B
authors.initials: B
authors.lastname: Yang
authors.forename: B
authors.initials: B
authors.lastname: Herman
authors.forename: K
authors.initials: K
authors.lastname: Jacobson
authors.forename: K K
authors.initials: KK
authors.lastname: Sulik
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D005732:Gangliosides / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009432:Neural Crest / Q000187:drug effects* / Q000502:physiology; D013045:Species Specificity
chemical_list: D002492:Central Nervous System Depressants; D005732:Gangliosides; C025447:sialogangliosides; D000431:Ethanol