Mg(2+)-deprivation enhances and Mg(2+)-supplementation diminishes the embryotoxic and teratogenic effects of Ni2+, Co2+, Zn2+, and Cd2+ for frog embryos in the FETAX assay

The influence of Mg2+ on the embryotoxicity and teratogenicity of Ni2+, Co2+, Zn2+, and Cd2+ for Xenopus embryos was studied by an adaptation of the FETAX protocol. In seven assays, 25 groups of embryos were grown from 5 to 101 hours post-fertilization in FETAX media that contained five graded MgCl2 concentrations (0, 6.2, 62, 620, or 6,200 mumol per L), with or without added NiCl2 (56 mumol per L), CoCl2 (1,800 mumol per L), ZnCl2 (300 mumol per L), or CdCl2 (18 mumol per L). In FETAX assays performed with the standard Mg2+ concentration (620 mumol per L), the incidence of malformations in control embryos averaged 5.4 (SD +/- 1.3) percent; the incidence of malformations in the controls was increased at low Mg2+ concentrations (32 +/- 7 percent at 62 mumol per L; 100 percent at greater than or equal to 6.2 mumol per L). The specified additions of Ni2+, Co2+, Zn2+, or Cd2+ caused death in < 10 under standard conditions (620 mumol Mg2+ per L). Mg(2+)-deprivation greatly enhanced and Mg(2+)-supplementation significantly reduced the incidence and severity of the teratogenic and embryotoxic effects of Ni2+, Co2+, Zn2+, and Cd2+ (p < 0.0001 by analysis of variance [ANOVA]). To explain these findings, the authors speculate that Mg2+ competes with the other divalent metal ions for a carrier mechanism involved in metal absorption or cellular uptake, or for binding to critical molecular targets.