The effect of benomyl on neurite outgrowth in mouse NB2A and human SH-SY5Y neuroblastoma cells in vitro.
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.
McLean
W G
WG
Department of Pharmacology, University of Liverpool, UK.
Holme
A D
AD
Janneh
O
O
Southgate
A
A
Howard
C V
CV
Reed
M G
MG
D000818:Animals; D001542:Benomyl / Q000633:toxicity*; D001932:Brain Neoplasms / Q000473:pathology* / Q000648:ultrastructure; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005659:Fungicides, Industrial / Q000633:toxicity*; D006801:Humans; D051379:Mice; D016501:Neurites / Q000187:drug effects* / Q000648:ultrastructure; D009447:Neuroblastoma / Q000473:pathology* / Q000648:ultrastructure; D051381:Rats; D014407:Tumor Cells, Cultured
D005659:Fungicides, Industrial; D001542:Benomyl