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Journal of Cell Science, Vol 11, 639-667, Copyright © 1972 by Company of Biologists

Submitted on January 11, 1972

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

E. H. MACINTYRE 1, C. J. WINTERSGILL 1, J. P. PERKINS 2, and A. E. VATTER 3

1 Department of Biological Sciences, University of Denver, Denver, Colorado 80210, U.S.A.
2 Department of Pharmacology, University of Colorado Medical Center, Denver, Colorado 80220, U.S.A.
3 Department of Pathology, University of Colorado Medical Center and the Webb-Waring Lung Institute, Denver, Colorado 80220, U.S.A.

N6, O2'-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.

Note:

Please address reprint requests to: Dr E. Macintyre, National Jewish Hospital Research Center, 3800 East Colfax Avenue, Denver, Colorado 80206, U.S.A.

Submitted on January 11, 1972




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© The Company of Biologists Ltd 1972