苯菌灵对体外培养的小鼠NB2A和人SH-SY5Y神经母细胞瘤细胞神经突生长的影响。

The effect of benomyl on neurite outgrowth in mouse NB2A and human SH-SY5Y neuroblastoma cells in vitro.

作者信息

McLean W G, Holme A D, Janneh O, Southgate A, Howard C V, Reed M G

机构信息

Department of Pharmacology, University of Liverpool, UK.

出版信息

Neurotoxicology. 1998 Aug-Oct;19(4-5):629-32.

PMID:9745922

Abstract

The commercial fungicide methyl 1-[(butylamino) carbonyl]-1H-benzimidazol-2-ylcarbamate (benomyl) is teratogenic in rats. Its mode of action is believed to be related to its ability to inhibit the polymerization of brain tubulin. In this study its effects were studied in cultured neuronal cells during differentiation and neurite outgrowth. Mouse NB2a and human SH-SY5Y neuroblastoma cells were induced to differentiate by addition of dibutyryl cyclic AMP and at the same time were exposed to various concentrations of benomyl. Benomyl significantly inhibited neurite outgrowth in both cell lines at concentrations of 10(-8) M and above with IC50 values of 5.9 x 10(-7) M and 1.0 x 10(-6) M in the NB2a and SH-SY5Y cells respectively. The results show that benomyl inhibits neuronal cell differentiation at concentrations likely to be achieved during the development of fetal abnormalities in rats in vivo.

摘要

商用杀真菌剂甲基 1-[(丁基氨基)羰基]-1H-苯并咪唑-2-基氨基甲酸酯（苯菌灵）对大鼠具有致畸性。其作用方式被认为与其抑制脑微管蛋白聚合的能力有关。在本研究中，研究了其在培养的神经元细胞分化和神经突生长过程中的作用。通过添加二丁酰环磷腺苷诱导小鼠NB2a和人SH-SY5Y神经母细胞瘤细胞分化，同时使其暴露于不同浓度的苯菌灵。苯菌灵在浓度为10^(-8) M及以上时显著抑制两种细胞系的神经突生长，在NB2a和SH-SY5Y细胞中的IC50值分别为5.9×10^(-7) M和1.0×10^(-6) M。结果表明，苯菌灵在大鼠体内胎儿发育异常过程中可能达到的浓度下抑制神经元细胞分化。