Biochemical and morphological study of adriamycin-induced changes in murine neuroblastoma cells

Cholinergic murine neuroblastoma cells, maintained in vitro, were exposed to a low concentration (0.4 micrograms/ml) of adriamycin. Morphologically the treated cells appeared to differentiate. The cell bodies increased in size from an average fixed cell body diameter of 7-13 to 25-40 micrometers, the cells developed long processes, became argyrophilic and the percentage of cells undergoing mitosis decreased relative to controls. Acetylcholine esterase activity increased in the drug-treated cells suggesting induction of differentiation. However, choline acetyltransferase activity and ganglioside composition remained unchanged. In addition, inoculation of mice with 2 x 10(5) viable drug-treated or control cells resulted in all of the mice developing neuroblastoma. No differences were observed in either the rate of tumor development or survival times. These results suggest that neuroblastoma cells may survive adriamycin treatment by becoming 'differentiated', ceasing cell division until conditions favor their undergoing another cell cycle.