Differentiation of mouse neuroblastoma cells in vitro and in vivo induced by cyclic adenosine monophosphate (cAMP).

The murine neuroblastoma appears to be a useful model for elucidating the mechanism of cellular differentiation. In tissue culture, MNB cells were induced to "irreversibly" differentiate into neuronal-like cells by DBcAMP alone or in combination with cAMP phosphodiesterase inhibitors: papaverine (Pap) and theophylline (Theo). Cells differentiated by DBcAMP, Pap, and Theo were no longer tumorgenic when reinoculated into animals of the host strain. In vivo, DBcAMP, Pap, and Theo caused a reduced tumor volume growth rate in animals with established tumors. Morphologically, this effect appears to be secondary to an arrest of cellular mitoses. Cells insensitive to these agents emerged after 3 to 4 days, and tumor growth accelerated to parallel the rate of the untreated tumors.