Restoration of Contact-Inhibited Growth to Transformed Cells by Dibutyryl Adenosine 3′:5′-Cyclic Monophosphate

Abstract

Spontaneously transformed and virallytransformed cells are restored to contact-inhibited growth by the addition of dibutyryl cyclic AMP to the nutrient medium. Theophylline, an inhibitor of the phosphodiesterase that degrades cyclic nucleotides, must also be present for maximal effect. Once the transformed cells reach a saturation density in the presence of the additives, release from the contact-inhibited state occurs upon removal of the dibutyryl cyclic AMP and theophylline from the medium. Agglutinability of the transformed cells by wheat-germ agglutinin (a monitor of architectural changes in the plasma membrane) is decreased by dibutyryl cyclic AMP-theophylline treatment, but increases again upon removal of the additives.

The actions of cyclic AMP, its butyryl derivatives and Na butyrate on the proliferation of malignant trophoblast cells in vitro

“…The effect of DB-cAMP on the cell proliferation was similar to that in some other cell lines, in which the compound appears to restore the contact-inhibited state of the cells, leading to a reduced saturation density (Teel and Hall, 1973;Sheppard, 1971). However, the present results suggest a similarity between the actions of DB-cAMP and butyrate, implying that DB-cAMP could have acted through degradation to butyrate.…”

The content and metabolism of cyclic adenosine 3', 5'-monophosphate and cyclic guanosine 3', 5'-monophosphate in adenocarcinoma of the human colon.

“…In the latter, cAMP rose three-to four-fold when cells reached confluency and growth ceased (15). Exogenous cAMP or agents that raised intracellular levels of cAMP restored contact inhibition and several normal morphologic characteristics to transformed cells (2)(3)(4)14). Similarly, cAMP has been shown to inhibit lymphocyte mitogenesis have lower cAMP levels during the S and M phases of their growth cycle than during G1 and G2 (35,36).…”

Adenovirus type 12 transformation involves loss of beta-adrenergic receptors and isoproterenol responsiveness.

“…Moreover, it has been suggested that some of the abnormal properties of transformed cells are related to alterations in cAMP metabolism (33). In keeping with this possibility, transformed cells treated with agents that elevate cAMP levels lose some of the properties of the transformed cell phenotype (15,16,31,39,43).…”