Wehner J M, Smolen A, Smolen T N, Murphy C
Fundam Appl Toxicol. 1985 Dec;5(6 Pt 1):1104-9. doi: 10.1016/0272-0590(85)90146-0.
The effect of a single dose of diisopropylfluorophosphate on acetylcholinesterase (AChE) activity was examined in mouse CNS reaggregate cultures. At 17-24 days in culture, reaggregates were treated with 0.6 mg/liter DFP for 15 min. The recovery of AChE activity was examined in culture. After treatment, 5.4 +/- 1.19% of control AChE activity remained. By 24 hr, 31.6 +/- 6.4% of control activity had returned and the recovery of activity was essentially complete by 7 days after treatment. Recovery of AChE activity after DFP treatment required protein synthesis, since there was no recovery in the presence of cycloheximide. After treatment with the reversible inhibitor, physostigmine at 0.5 mg/ml, recovery of AChE activity was complete within 24 hr after treatment. These results indicate that CNS reaggregate cultures not only express differentiated functions of the CNS, but also have the capacity to turn over proteins, and thus may provide a good model system in which to examine mechanisms of toxicity.
在小鼠中枢神经系统再聚集培养物中检测了单剂量二异丙基氟磷酸酯对乙酰胆碱酯酶(AChE)活性的影响。在培养17 - 24天时,用0.6毫克/升的二异丙基氟磷酸酯(DFP)处理再聚集物15分钟。在培养物中检测AChE活性的恢复情况。处理后,对照AChE活性仅剩余5.4±1.19%。到24小时时,对照活性的31.6±6.4%已经恢复,并且在处理后7天活性基本完全恢复。DFP处理后AChE活性的恢复需要蛋白质合成,因为在存在环己酰亚胺的情况下没有恢复。在用0.5毫克/毫升的可逆抑制剂毒扁豆碱处理后,AChE活性在处理后24小时内完全恢复。这些结果表明,中枢神经系统再聚集培养物不仅表达中枢神经系统的分化功能,而且具有蛋白质更新的能力,因此可能提供一个良好的模型系统来研究毒性机制。