Hopfer S M, Plowman M C, Sweeney K R, Bantle J A, Sunderman F W
Department of Laboratory Medicine, School of Medicine, University of Connecticut, Farmington 06032.
Biol Trace Elem Res. 1991 Jun;29(3):203-16. doi: 10.1007/BF03032678.
The teratogenicity of Ni2+ was tested by the FETAX (Frog Embryo Teratogenesis Assay: Xenopus) procedure in the South African frog, Xenopus laevis. In seven assays, beginning at 5 h postfertilization, groups of Xenopus embryos were incubated for 96 h in media that contained Ni2+ (added as NiCl2) at concentrations ranging from 1 x 10(-7) to 3 x 10(-3) mol/L; control groups were incubated in the same medium without added NiCl2. At 101 h postfertilization, surviving embryos were counted, fixed in formalin, and examined by microscopy to determine their developmental stages, malformations, and head-to-tail lengths. In control embryos, survival was greater than or equal to 95% and malformations were less than or equal to 7%. Malformations were found in greater than 95% of embryos exposed to Ni2+ concentrations greater than or equal to 5.6 mumol/L. The most frequent malformations in Ni(2+)-exposed embryos were ocular, skeletal, and intestinal deformities; less common malformations included facial, cardiac, and integumentary deformities. Other abnormalities, not categorized as malformations, included stunted growth, dermal hypopigmentation, and coelomic effusions or hemorrhages. The median embryolethal concentration (LC50) of Ni2+ was 365 (SE +/- 9) mumol/L; the median teratogenic concentration (EC50) was 2.5 (SE +/- 0.1) mumol/L; the Teratogenic Index (TI = LC50/EC50) was 147 (SE +/- 5), indicating that Ni2+ is a potent teratogen for Xenopus laevis. Experiments in which Ni(2+)-exposures were limited to specific 24 h periods showed that Xenopus embryos were most susceptible to Ni(2+)-induced malformations on the second and third days of life, during the most active period of organogenesis.
采用FETAX(非洲爪蟾胚胎致畸试验)程序,在南非爪蟾(非洲爪蟾)中测试了Ni2+的致畸性。在七次试验中,从受精后5小时开始,将非洲爪蟾胚胎分组,在含有浓度范围为1×10(-7)至3×10(-3)mol/L的Ni2+(以NiCl2形式添加)的培养基中孵育96小时;对照组在不添加NiCl2的相同培养基中孵育。在受精后101小时,对存活的胚胎进行计数,用福尔马林固定,并通过显微镜检查以确定其发育阶段、畸形情况和头尾长度。在对照胚胎中,存活率大于或等于95%,畸形率小于或等于7%。在暴露于浓度大于或等于5.6μmol/L的Ni2+的胚胎中,超过95%出现畸形。暴露于Ni(2+)的胚胎中最常见的畸形是眼部、骨骼和肠道畸形;较不常见的畸形包括面部、心脏和皮肤畸形。其他未归类为畸形的异常情况包括生长发育迟缓、皮肤色素减退以及体腔积液或出血。Ni2+的半数胚胎致死浓度(LC50)为365(标准误±9)μmol/L;半数致畸浓度(EC50)为2.5(标准误±0.1)μmol/L;致畸指数(TI = LC50/EC50)为147(标准误±5),表明Ni2+是非洲爪蟾的一种强效致畸剂。将Ni(2+)暴露限制在特定24小时时间段的实验表明,非洲爪蟾胚胎在生命的第二天和第三天,即器官发生最活跃的时期,对Ni(2+)诱导的畸形最为敏感。