Oohira A, Nogami H
Teratology. 1978 Aug;18(1):63-70. doi: 10.1002/tera.1420180110.
The teratogenicity of 2,2'-dipyridyl (DIP), a chelator for ferrous iron, was investigated by administration of single dose of 60 or 75 mg/kg intraperitoneally to pregnant SD rats on days 11.5-14.5. Fetuses examined on day 21 were decreased in weight, and had defects chiefly in the limb. The type and incidence of limb defects differed according to day of treatment. Digital malformations in the forelimb and long-bone defects in the hindlimb were produced with high incidence by treatment on day 12.5, and the frequency of digital malformations in the hindlimb was increased by treatment on day 13.5. Light and electron microscopic examinations revealed the delay of mesenchymal condensation and destruction of mesenchymal cells in the forelimb bud in the early stage after day 12.5 treatment. The normal increase of DNA, protein, collagen and glycosaminoglycan contents in the forelimb bud was markedly inhibited by the treatment. The incorporation activities for [14C]proline and [14C]glucosamine of the forelimb bud were reduced to 50-60% of the control. These results indicate that DIP has potent teratogenic and cytotoxic effects on the development of the rat limb bud.
通过在妊娠第11.5至14.5天对妊娠SD大鼠腹腔注射60或75mg/kg的单剂量，研究了亚铁螯合剂2,2'-联吡啶（DIP）的致畸性。在第21天检查的胎儿体重减轻，主要肢体存在缺陷。肢体缺陷的类型和发生率因治疗天数而异。在第12.5天治疗可导致前肢指畸形和后肢长骨缺陷的高发生率，在第13.5天治疗会增加后肢指畸形的频率。光镜和电镜检查显示，在第12.5天治疗后的早期，前肢芽中的间充质凝聚延迟和间充质细胞破坏。该治疗显著抑制了前肢芽中DNA、蛋白质、胶原蛋白和糖胺聚糖含量的正常增加。前肢芽对[14C]脯氨酸和[14C]氨基葡萄糖的掺入活性降低至对照的50-60%。这些结果表明，DIP对大鼠肢体芽的发育具有强大的致畸和细胞毒性作用。
