ETHANOL-INDUCED TERATOGENESIS - FREE-RADICAL DAMAGE AS A POSSIBLE MECHANISM

To investigate the possibility of a free radical mechanism for ethanol -induced teratogenesis, gestational day 8 mouse embryos were exposed f or 6 hr in whole embryo culture to a teratogenic dosage of ethanol alo ne (500 mg%) or in conjunction with an antioxidant, superoxide dismuta se (SOD; 300 U/ml). For subsequent analysis, some embryos were examine d at the end of this 6-hr period, while others were removed to control medium and cultured for an additional time period. Ethanol exposure r esulted in increased superoxide anion generation and increased lipid p eroxidation (as noted 6 hr after initial ethanol exposure) and in exce ssive cell death (as noted 12 hr after initial exposure) in the embryo s. Following a total of 36 hr in culture, a high incidence of malforma tion, including failure of the anterior neural tube to close in 63% of the ethanol-exposed embryos, was noted. The ethanol-induced superoxid e anion generation, lipid peroxidation, excessive cell death, and dysm orphogenesis were diminished in embryos co-treated with SOD, suggestin g that the teratogenicity of ethanol is mediated, at least in part, by free radical damage. (C) 1995 Wiley-Liss, Inc.