A further study on the morphology and biochemistry of x-ray and dibutyryl cyclic AMP-induced differentiated neuroblastoma cells in culture

Dibutyryl cyclic AMP-induced morphological differentiation of mouse neuroblastoma cells in culture required the synthesis of new protein but not of new RNA. An appreciable increase in RNA synthesis, a slight increase in protein synthesis and a marked decrease in DNA synthesis occurred in the dibutyryl cyclic AMP-induced differentiated cells. Tyrosine hydroxylase activity which is barely detectable in the control neuroblastoma culture markedly increased after treatment with dibutyryl cyclic AMP. Sodium butyrate, which inhibited cell division without causing morphological differentiation also increased tyrosine hydroxylase activity, but to a lesser degree. 3′5′ Cyclic AMP and 5′AMP which inhibited cell division without causing morphological differentiation did not increase the enzyme activity.X-irradiation produced inhibition of cell division and morphological differentiation similar to that observed with dibutyryl cyclic AMP, but the tyrosine hydroxylase activity did not increase. The irradiated cells, nevertheless, retained the potential to manifest increased tyrosine hydroxylase levels upon subsequent exposure to either dibutyryl cyclic AMP or sodium butyrate. The present data suggest that increased tyrosine hydroxylase levels in neuroblastoma cells is not inextricably linked to morphological changes which are presumed to reflect cellular differentiation.