Cytosine arabinoside differentially alters survival and neurite outgrowth of neuronal PC12 cells.

Cytosine arabinoside, a potent antimitotic agent, is used clinically as an anticancer drug with the side effect of severe neurotoxicity. Earlier reports suggested that this agent blocks the signaling pathway of nerve growth factor in sympathetic neurons, which results in neuronal death. The present study demonstrated that neuronal PC12 cells deprived of nerve growth factor showed a decrease of neurite outgrowth, which was not seen in cytosine arabinoside-treated neuronal PC12 cells, suggesting that this agent may not interfere with the part of the NGF signaling pathway that leads to neurite outgrowth. On the other hand, treatment of neuronal PC12 cells with cytosine arabinoside led to a dose- and time-dependent decrease of viability. These results suggest that there is a distinction between the neurite outgrowth and the survival promoting activities of nerve growth factor.