Abstract
Tricresyl phosphate (1 μg/ml) inhibited the outgrowth of axon-like processes in mouse N2a neuroblastoma and rat PC12 pheochromocytoma cell lines induced to differentiate by serum withdrawal and nerve growth factor addition, respectively. By contrast, it had no effect on the outgrowth of processes by rat C6 glioma cells induced to differentiate with sodium butyrate. The effect on axon outgrowth in the two neuronal cell lines correlated with altered distribution of neurofilament proteins, as determined by indirect immunofluorescence with monoclonal antibody RMd09. Western blots of neuronal cell extracts probed with the same antibody revealed decreased cross-reactivity after exposure to tricresyl phosphate. The results suggest that tricresyl phosphate has a selective effect on neuronal cell differentiation, which involves impaired axon outgrowth, reduced levels of the neurofilament heavy chain and disruption of the neurofilament network.
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