Jacobs A J, Maniscalco W M, Finkelstein J N
Toxicol Appl Pharmacol. 1986 Dec;86(3):362-71. doi: 10.1016/0041-008x(86)90363-7.
High fetal and neonatal brain levels of methyl mercury (MeHg) have been associated with the abnormal migration of neurons within the cerebellar and cerebral cortices. How MeHg interferes with cellular proliferation, migration, and differentiation is poorly understood. In this study, a cell recognition/cohesion assay based on the ability of dissociated neonatal mouse cerebellar cells to reaggregate was used to test whether MeHg exposure could disrupt cell surface recognition. Reaggregation of dissociated cells was monitored by measuring diameters from low-power photomicrographs. Exposure to 4 mg/kg body wt methylmercuric chloride (MeHgCl) 24 hr prior to the isolation of 3 days postnatal cerebellar cells altered the pattern of reaggregate growth. Between 25 and 51 hr in vitro (hiv), the exposed reaggregates grew at a faster rate than controls. Freshly isolated cells exposed in vitro to 0, 0.5, 1.0, and 4.0 microM MeHgCl initially exhibited a dose-related inhibition in reaggregate growth with an IC50 of 1.5 microM at 24 hiv. Following initial inhibition, exposed groups showed a dose-dependent acceleration in reaggregation similar to that found following in vivo exposure. In contrast, in vitro exposure to cycloheximide resulted in only a dose-related inhibition of reaggregation. No acceleration in growth rate was seen. Colchicine exposure produced no initial inhibition but appeared to mimic the long-term effects seen with both in vivo and in vitro MeHgCl exposure. These studies suggest that MeHgCl alters cerebellar cell recognition through a complex mechanism initially involving depressed synthesis of specific proteins followed by alterations in microtubules. Both effects may involve a disruption in the arrangement of specific cell surface recognition molecules.
胎儿和新生儿大脑中高浓度的甲基汞（MeHg）与小脑和大脑皮质内神经元的异常迁移有关。目前对MeHg如何干扰细胞增殖、迁移和分化了解甚少。在本研究中，基于新生小鼠小脑细胞解离后重新聚集的能力建立了细胞识别/黏附试验，以测试MeHg暴露是否会破坏细胞表面识别。通过测量低倍显微照片的直径来监测解离细胞的重新聚集情况。在分离出生后3天的小脑细胞前24小时，给小鼠暴露4mg/kg体重的氯化甲基汞（MeHgCl），这改变了重新聚集生长的模式。在体外25至51小时（hiv）之间，暴露组的重新聚集体生长速度比对照组快。体外暴露于0、0.5、1.0和4.0μM MeHgCl的新鲜分离细胞最初在重新聚集生长中表现出剂量相关的抑制，在24hiv时IC50为1.5μM。在最初的抑制之后，暴露组在重新聚集中表现出剂量依赖性的加速，类似于体内暴露后的情况。相比之下，体外暴露于环己酰亚胺仅导致重新聚集的剂量相关抑制。未观察到生长速度的加速。秋水仙碱暴露未产生初始抑制，但似乎模拟了体内和体外MeHgCl暴露所观察到的长期效应。这些研究表明，MeHgCl通过一种复杂的机制改变小脑细胞识别，该机制最初涉及特定蛋白质合成的抑制，随后是微管的改变。这两种效应可能都涉及特定细胞表面识别分子排列的破坏。
