The Responses in Culture of Human Tumour Astrocytes and Neuroblasts to N6,O2′-Dibutyryl Adenosine 3′,5′-Monophosphoric Acid

Abstract

N⁶, O^2'-dibutyryl cyclic AMP (DBcAMP) (3 x 10^-4 M) causes reproducible changes in the morphology, growth rate and terminal cell density of 3 different types of human tumour cells grown in culture. Human tumour astrocyte lines 1181N1 and EH-118MG show generalized ablation of membrane systems when grown in the presence of this cyclic AMP analogue. This is not consistent with differentiation; it may be a toxic effect but possibly represents the response of these cell types to DBcAMP. These cells also grow more slowly and to lower terminal cell densities as a function of the concentration of DBcAMP. Although the growth kinetics demonstrate a return of these malignant cells to a state of density-dependent growth, micrographic analyses of inter-cellular relationships reveal that the cells still grow in overlapping patterns. Thus as judged by the commonly accepted criteria, DBcAMP does not induce contact inhibition of growth. All observed changes induced by the presence of DBcAMP are rapidly and completely reversed upon its removal from the growth medium. Human neuroblasts (NB1) grown in the presence of DBcAMP show irreversible morphological changes and the rate and extent of cell division is reduced. There is marked hyperplasia of intracytoplasmic microfilaments, which is considered consistent with differentiation.