Cyclic AMP, ATP and cell contact

Abstract

DENSITY-DEPENDENT¹ or contact-inhibited² cells stop dividing when they reach confluency; however, transformed cells do not exhibit this type of growth control³. Several experiments suggest that adenosine 3′,5′-cyclic monophosphate (cyclic AMP) is involved in regulating the cell division of cultured fibroblasts. The dibutyryl derivative of cyclic AMP inhibits proliferation of transformed cells⁴, and the steady state levels of cyclic AMP in normal density-dependent fibroblasts are higher than the corresponding virus and spontaneous transformed cell lines^5,6. There are, however, discrepancies between experiments which have attempted to compare the cyclic AMP levels of logarithmically growing with quiescent, density-inhibited 3T3 cells. Experiments in our laboratory showed that cyclic AMP levels of 3T3 cells do not change over the cell density of 1 × 10⁴ – 6 × 10⁴ cells per cm² (ref. 5). These results have been confirmed by others using the same cell system⁷. Otten et al.^6,8, however, reported that cyclic AMP levels of logarithmically growing 3T3 cells are lower than those of confluent, quiescent cells; Heidrick and Ryan⁹ reported similar results using L cells.