Restoration of Several Morphological Characteristics of Normal Fibroblasts in Sarcoma Cells Treated with Adenosine-3′:5′-Cyclic Monophosphate and Its Derivatives

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Abstract
Sarcoma cells growing in tissue culture have morphological and growth characteristics different than normal fibroblasts. Several of the morphological characteristics of normal fibroblasts are regained when the cells are incubated with dibutyryl-cyclic AMP or butyryl-cyclic AMP (0.1-1 mM), or cyclic AMP (3 mM) plus theophylline (1 mM), but not with ATP, ADP, AMP, adenine, or adenosine (1-7 mM). The cell bodies become elongated; distinct narrow processes are formed. With prolonged incubation, the cells show less tendency to pile up or become polygonal. Further, L-929 and Rous sarcomatransformed hamster cells orient in parallel arrays characteristic of contact inhibition. The cells retain their altered morphology as long as the butyryl-cyclic AMP is present, but revert after its removal. Experiments with cycloheximide, puromycin, and actinomycin D indicate that protein Synthesis, but not RNA synthesis, is required for the response. Microtubular proteins may be involved. No response is observed with normal fibroblasts or with various epithelial cells. The data suggest that cyclic AMP may be an important factor in the determination of morphology of normal fibroblasts and this function may be lost or altered during transformation.