Differentiation of rat pheochromocytoma cells by fomitellic acids, specific DNA polymerase inhibitors.

Fomitellic acid (FA) A and B are specific inhibitors of DNA polymerase alpha and beta. They showed cytotoxicity against rat pheochromocytoma cells (PC-12 cells) in a concentration-dependent manner. However, after PC-12 cells were cultivated with low concentrations of FAs, the cells extended neurites in greater degree similar to the cells cultivated with nerve growth factor. Another DNA polymerase alpha inhibitor, aphidicolin, also induced neurite outgrowth. Furthermore, PC-12 cells were strongly immunostained with anti-alpha-tubulin or anti-tau antibody after the treatment with FAs. These results suggest that weak inhibition of DNA polymerase activity induces the neurite outgrowth in PC-12 cells.