McNutt T L, Harris C
Department of Environmental and Industrial Health, University of Michigan, Ann Arbor 48109-2029.
Reprod Toxicol. 1994 Jul-Aug;8(4):351-62. doi: 10.1016/0890-6238(94)90051-5.
The lindane embryotoxicity and associated changes in cysteine (CYS) and glutathione (GSH) status have been investigated in the early organogenesis-stage rat conceptus utilizing whole embryo culture techniques. Direct exposure of gestational day 10 (GD 10) conceptuses to lindane (50, 100, 200, 300, and 400 microM) in the culture medium resulted in a dose- and time-dependent increase in mortality (88% at 400 microM), frequency, and severity of malformations and in decreased growth parameters. Protein and DNA contents of embryo and visceral yolk sac (VYS), likewise decreased significantly as lindane concentrations increased. Lindane exposures greater than 100 microM produced abnormal axial rotation, pooled blood on lateral cephalic surfaces, cephalic edema, and decreased VYS vasculature. Histologic sections showed a variety of abnormalities, including distended anterior cardinal veins, thinning of the neuroepithelium in forebrain and hindbrain regions, and abnormal branchial arch development. CYS and GSH levels in the VYS were not significantly affected by 100 microM lindane exposure during a 5-h incubation period on GD 10 and GD 11. In contrast, CYS and GSH levels in lindane-exposed embryos remained unchanged while control levels continued to increase with gestational age. At 5 h, treated embryos showed a significant depletion of CYS (GD 10, 22%; GD 11, 35%) and GSH (GD 10, 41%; GD 11, 24%) relative to controls. Selective lindane-induced depletion of embryonic GSH suggests involvement of the glutathione redox cycle in lindane embryotoxicity.
利用全胚胎培养技术，在器官形成早期阶段的大鼠胚胎中研究了林丹的胚胎毒性以及与之相关的半胱氨酸（CYS）和谷胱甘肽（GSH）状态的变化。将妊娠第10天（GD 10）的胚胎直接暴露于培养基中的林丹（50、100、200、300和400微摩尔），导致死亡率（400微摩尔时为88%）、畸形频率和严重程度呈剂量和时间依赖性增加，同时生长参数降低。随着林丹浓度的增加，胚胎和内脏卵黄囊（VYS）的蛋白质和DNA含量同样显著下降。林丹暴露量大于100微摩尔会导致轴向旋转异常、侧头表面血液积聚、头部水肿以及VYS血管减少。组织学切片显示出多种异常，包括前主静脉扩张、前脑和后脑区域神经上皮变薄以及鳃弓发育异常。在GD 10和GD 11的5小时孵育期内，100微摩尔林丹暴露对VYS中的CYS和GSH水平没有显著影响。相比之下，暴露于林丹的胚胎中的CYS和GSH水平保持不变，而对照水平则随着胎龄继续增加。在5小时时，与对照组相比，处理过的胚胎显示CYS（GD 10时为22%；GD 11时为35%）和GSH（GD 10时为41%；GD 11时为24%）显著耗竭。林丹选择性诱导的胚胎GSH耗竭表明谷胱甘肽氧化还原循环参与了林丹的胚胎毒性。
