Saillenfait A M, Payan J P, Sabate J P, Langonne I, Fabry J P, Beydon D
Institut National de Recherche et de Sécurité, Vandoeuvre, France.
Toxicol Appl Pharmacol. 1993 Dec;123(2):299-308. doi: 10.1006/taap.1993.1249.
To investigate the effects of amino acids on the embryotoxicity and placental transfer of nickel chloride (NiCl2), Day 10 rat embryos were cultured in rat serum medium containing NiCl2 or 63NiCl2 (0.34 or 0.68 mM Ni), with or without L-histidine (2 mM), L-aspartic acid, glycine (2 or 8 mM), or L-cysteine (2 mM). After 26 hr, conceptuses were assessed for survival, growth and development, and malformations. The 63Ni contents of embryos and yolk sacs and the extent of 63Ni binding to the proteins of the culture medium were also determined. NiCl2 alone did not affect the embryonic development at 0.34 mM and caused growth retardation and brain and caudal abnormalities at 0.68 mM. Coincubation of L-histidine with 0.34 mM Ni increased Ni concentrations in embryonic tissues compared to 0.34 mM 63Ni alone, but did not elicit NiCl2 embryotoxicity. Coincubation of L-cysteine with 0.34 mM Ni elicited growth retardation and brain abnormalities caused by NiCl2 and increased yolk sac concentrations of 63Ni compared to 0.34 mM 63Ni alone. In contrast, coincubation of L-histidine, L-cysteine, or L-aspartic acid with 0.68 mM Ni reduced the growth retardation and the incidence and/or severity of brain defects caused by NiCl2 and decreased the concentrations of 63Ni in the yolk sacs, compared to 0.68 mM 63Ni alone. L-Histidine also reduced the percentage of NiCl2-elicited caudal defects. Coincubation with glycine did not NiCl2-elicited caudal defects. Coincubation with glycine did not affect the embryotoxic profile, nor the placental transfer of NiCl2. In the presence of L-histidine, L-cysteine, or L-aspartic acid, there was a shift of 63Ni binding from the high-molecular-weight proteins of the culture medium to the low-molecular-weight fraction. Thus, specific extracellular amino acids can modulate the embryotoxicity and placental transfer of NiCl2 in vitro. The pattern of this modulation is dependent on the concentration of NiCl2, as well as on the amino acid.
为研究氨基酸对氯化镍（NiCl₂）胚胎毒性及胎盘转运的影响，将妊娠第10天的大鼠胚胎培养于含NiCl₂或⁶³NiCl₂（镍浓度分别为0.34或0.68 mM）的大鼠血清培养基中，培养基中还添加或不添加L - 组氨酸（2 mM）、L - 天冬氨酸、甘氨酸（2或8 mM）或L - 半胱氨酸（2 mM）。26小时后，评估胚胎的存活、生长发育及畸形情况。同时测定胚胎和卵黄囊中⁶³Ni的含量以及⁶³Ni与培养基中蛋白质的结合程度。单独的NiCl₂在0.34 mM时不影响胚胎发育，在0.68 mM时导致生长迟缓以及脑和尾部异常。与0.34 mM Ni单独培养相比，L - 组氨酸与0.34 mM Ni共同培养可增加胚胎组织中的镍浓度，但未引发NiCl₂胚胎毒性。L - 半胱氨酸与0.34 mM Ni共同培养引发了NiCl₂所致的生长迟缓和脑异常，且与0.34 mM⁶³Ni单独培养相比，增加了卵黄囊中⁶³Ni的浓度。相反，与0.68 mM Ni单独培养相比，L - 组氨酸、L - 半胱氨酸或L - 天冬氨酸与0.68 mM Ni共同培养可减轻NiCl₂所致的生长迟缓以及脑缺陷的发生率和/或严重程度，并降低卵黄囊中⁶³Ni的浓度。L - 组氨酸还降低了NiCl₂所致尾部缺陷的比例。与甘氨酸共同培养未影响NiCl₂所致的尾部缺陷，也未影响NiCl₂的胚胎毒性谱及胎盘转运。在L - 组氨酸、L - 半胱氨酸或L - 天冬氨酸存在的情况下，⁶³Ni的结合从培养基中的高分子量蛋白质转移至低分子量部分。因此，特定的细胞外氨基酸可在体外调节NiCl₂的胚胎毒性及胎盘转运。这种调节模式取决于NiCl₂的浓度以及氨基酸种类。
