TRICRESYL PHOSPHATE INHIBITS THE FORMATION OF AXON-LIKE PROCESSES ANDDISRUPTS NEUROFILAMENTS IN CULTURED MOUSE N2A AND RAT PC12 CELLS

Tricresyl phosphate (1 mu g/ml) inhibited the outgrowth of axon-like p rocesses in mouse N2a neuroblastoma and rat PC12 pheochromocytoma cell lines induced to differentiate by serum withdrawal and nerve growth f actor addition, respectively. By contrast, it had no effect on the out growth of processes by rat C6 glioma cells induced to differentiate wi th sodium butyrate. The effect on axon outgrowth in the two neuronal c ell lines correlated with altered distribution of neurofilament protei ns, as determined by indirect immunofluorescence with monoclonal antib ody RMd09. Western blots of neuronal cell extracts probed with the sam e antibody revealed decreased cross-reactivity after exposure to tricr esyl phosphate. The results suggest that tricresyl phosphate has a sel ective effect on neuronal cell differentiation, which involves impaire d axon outgrowth, reduced levels of the neurofilament heavy chain and disruption of the neurofilament network. (C) 1998 Elsevier Science Ire land Ltd.