Levels of Cyclic AMP in Sparse and Dense Cultures of Growing and Quiescent 3T3 Cells

Abstract

3′ 5′-CYCLIC adenosine monophosphate (cAMP) has been reported to be involved in the regulation of cellular growth^1–5. cAMP levels are low in growing 3T3 cells whereas they are increased in resting cells in confluent cultures⁵. SV40 or polyoma virus transformed 3T3 cells as well as 3T6 and BHK cells, which reach high cell densities and do not become quiescent, are characterized by a low serum requirement and low levels of cAMP⁶ (W. Seifert, unpublished results). Therefore, it has been suggested that the growth pattern of normal cells (for example, density dependent cessation of growth) is controlled by intracellular cAMP levels^2,5,6: high cellular levels of cAMP are considered to be growth inhibitory while depressed cellular cAMP levels may lead to a continuation of growth^1,2,5. It has been suggested^1,8 that the levels of cAMP in resting cells are increased as a consequence of contact between cells which may lead to a stimulation of the membrane bound adenyl cyclase. A negative signal which would lead to the inhibition of DNA synthesis as a consequence of cell-cell contact has been suggested⁷. Evidence from studies on inhibition of cell growth by (But)₂cAMP and/or theophylline points to cAMP as a possible mediator^1,2,8. Serum, however, antagonizes the growth inhibiting effect of (But)₂cAMP^9,10.