Inhibition of Growth and DNA Synthesis in Cell Cultures by Cyclic Amp

1974 ◽  
Vol 16 (2) ◽  
pp. 301-307
Author(s):  
P. EKER
Keyword(s):  
Cyclic Amp ◽  
Dna Synthesis ◽  
Cell Cultures ◽  
Degradation Products ◽  
Liver Cells ◽  
Soluble Cell ◽  
Inhibition Of Growth ◽  
Insoluble Material ◽  
Rna And Protein Synthesis ◽  
Soluble Cell Fraction

Cyclic AMP (0.1 to 1 mM) was found to inhibit the growth of human liver cells in monolayer cultures. Significant amounts of degradation products were not detected in the medium indicating that the growth-inhibiting effect was associated with the intact cyclic nucleotide. DNA synthesis in the liver cell cultures, as measured by thymidine incorporation into acid-insoluble material, was markedly inhibited by cyclic AMP. RNA and protein synthesis were not significantly affected. Cyclic AMP induced a considerable increase in the cellular uptake of thymidine and uridine from the medium. When the liver cells were incubated in medium containing radioactive cyclic AMP, no labelled cyclic AMP could be detected in the acid-soluble cell fraction by chromatographic analysis. It is suggested that cyclic AMP does not enter the liver cells, but that its action on growth and DNA synthesis is somehow mediated through an interaction with the cell surface.

MEDIATION BY CALCICALMODULIN AND CYCLIC AMP OF TUMOR PROMOTER-INDUCED DNA SYNTHESIS IN CALCIUM-DEPRIVED RAT LIVER CELLS

1982 ◽  
pp. 417-431 ◽  
Author(s):  
Alton L. Boynton ◽  
Leonard P. Kleine ◽  
Jon P. Durkin ◽  
James F. Whitfield ◽  
Alan Jones
Keyword(s):  
Cyclic Amp ◽  
Dna Synthesis ◽  
Rat Liver ◽  
Liver Cells ◽  
Tumor Promoter ◽  
Rat Liver Cells

scholarly journals The role of adenosine 3′:5′-cyclic monophosphate in the division of WI 38 cells. The cellular response to prostaglandin E1 and the effects of an cyclic adenosine 3′:5′-cyclic monophosphate analogue and prostaglandin E1 on cell division

1974 ◽  
Vol 142 (2) ◽  
pp. 339-344 ◽  
Author(s):  
Mary J. Kurtz ◽  
Peter Polgar ◽  
Linda Taylor ◽  
Alexander M. Rutenburg
Keyword(s):  
Cyclic Amp ◽  
Dna Synthesis ◽  
Cellular Response ◽  
Prostaglandin E1 ◽  
Culture Media ◽  
Marked Variation ◽  
Cyclic Monophosphate ◽  
Inhibition Of Growth ◽  
Lower Cell Density

Inhibition of growth and DNA synthesis was observed in WI 38 cells incubated with 8-methylthioadenosine 3′:5′-cyclic monophosphate or prostaglandin E1. The effect of both compounds on cell growth was reversible. On removal of these compounds from culture media the cells initiated DNA synthesis and divided. In addition, prostaglandin E1 stimulated cyclic AMP formation in these cells to over 40 times the normal basal value. The increase in cyclic AMP concentration in WI 38 cells after addition of prostaglandin E1 showed a marked variation. Cells that had recently been treated with trypsin and plated at a lower cell density exhibited a smaller response to addition of prostaglandin E1 than cells that had divided and reached confluence.

scholarly journals Inhibition of DNA synthesis in SV3T3 cultures by isolated 3T3 plasma membranes.

1983 ◽  
Vol 97 (1) ◽  
pp. 276-279 ◽  
Author(s):  
S W Peterson ◽  
V Lerch
Keyword(s):  
Plasma Membrane ◽  
Dna Synthesis ◽  
Cell Cultures ◽  
Plasma Membranes ◽  
Inhibitory Effect ◽  
Density Dependent ◽  
Inhibition Of Growth ◽  
Dependent Inhibition ◽  
Membrane Components ◽  
Inhibition Of Dna Synthesis

3T3 plasma membranes were added to subconfluent cultures of SV3T3 cells in the presence of fusogens. If this protocol results in the introduction into the SV3T3 cell membrane of 3T3 plasma membrane components responsible for density-dependent inhibition of growth, then the SV3T3 cell cultures would be expected to show decreased rates of DNA synthesis as they approach confluence. Results of these experiments indicate that rates of DNA synthesis in SV3T3 cultures so treated were as much as 63% less than in untreated controls. This effect could not be attributed to the fusogens or to the 3T3 plasma membranes alone. This growth-inhibitory effect is specific for 3T3 membranes and is not observed when SV3T3 plasma membranes are fused with SV3T3 cell cultures. These data support the hypothesis that one aspect of the loss of density-dependent inhibition of growth in SV3T3 cells is a deletion or alteration in plasma membrane components and, further, that density-dependent inhibition of growth can be in part restored to SV3T3 cell cultures by fusing the cells with 3T3 plasma membranes.

scholarly journals REGULATION OF PHOSPHOENOLPYRUVATE CARBOXYKINASE AND TYROSINE TRANSAMINASE IN HEPATOMA CELL CULTURES

1974 ◽  
Vol 60 (1) ◽  
pp. 181-191 ◽  
Author(s):  
Han van Rijn ◽  
Marinus M. Bevers ◽  
Roeland van Wijk ◽  
Wesley D. Wicks
Keyword(s):  
Growth Rate ◽  
Cyclic Amp ◽  
Dna Synthesis ◽  
Cell Cultures ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Hepatoma Cell ◽  
Transaminase Activity ◽  
Dibutyryl Cyclic Amp ◽  
Tyrosine Transaminase ◽  
Htc Cells

The ability of N6, O2'-dibutyryl cyclic AMP (DBcAMP) to regulate a number of metabolic events in four lines of cultured rat hepatomas has been examined. Although dexamethasone induces tyrosine transaminase in all four lines, DBcAMP induces this enzyme normally only in H35 cells. A slight increase in transaminase activity was seen with MH1C1 cells and HTC cells, but no effect was detectable in RLC cells. In contrast, phosphoenolpyruvate carboxykinase activity is increased by both agents in H35 and MH1C1 cells, but neither had any effect in HTC or RLC cells. DBcAMP caused a rapid inhibition of the growth rate and DNA synthesis and an increase in protein content in both H35 and MH1C1 cells but not in HTC or RLC cells. The effect of DBcAMP on DNA synthesis in MH1C1 cells could be reversed by deoxycytidine as is also the case with H35 cells. The resistance of HTC and RLC cells to DBcAMP was not due to reduced uptake or deacylation as judged by studies with [3H]DBcAMP. The cyclic nucleotide appears to enter the cells by passive diffusion as the intracellular concentration approaches that in the medium within 30–60 min. Possible explanations for the differential responses observed are discussed.

scholarly journals Stimulation by defined parathyroid hormone fragments of cell proliferation in skeletal-derived cell cultures

1990 ◽  
Vol 272 (3) ◽  
pp. 781-785 ◽  
Author(s):  
D Sömjen ◽  
I Binderman ◽  
K D Schlüter ◽  
E Wingender ◽  
H Mayer ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Cyclic Amp ◽  
Dna Synthesis ◽  
Cell Cultures ◽  
Thymidine Incorporation ◽  
Bone Cells ◽  
Functional Domain ◽  
Independent Manner ◽  
Rat Calvaria ◽  
Calvaria Cell

We have reported previously that parathyroid hormone (PTH) acts on cultured bone cells to stimulate creatine kinase (CK) activity and [3H]thymidine incorporation into DNA via phosphoinositide turnover, in addition to its other actions via increased cyclic AMP production. We also found that mid-region fragments of PTH stimulate [3H]thymidine incorporation into avian chondrocytes. In the present study of mammalian systems, we demonstrate differential effects of defined synthetic PTH fragments on CK activity and DNA synthesis, as compared with cyclic AMP production, in osteoblast-enriched embryonic rat calvaria cell cultures, in an osteoblast-like clone of rat osteosarcoma cells (ROS 17/2.8) and in chondroblasts from rat epiphysial cartilage cell cultures. Unlike full-length bovine (b)PTH-(1-84) or the fully effective shorter fragment human (h)PTH-(1-34), fragments lacking the N-terminal region of the hormone did not increase cyclic AMP formation, whereas they did stimulate increases in both DNA synthesis and CK activity. Moreover, the PTH fragment hPTH-(28-48) at 10 microM inhibited the increase in cyclic AMP caused by 10 nM-bPTH-(1-84). The increase of CK activity in ROS 17/2.8 cells caused by bPTH-(1-84) or hPTH-(28-48) was completely inhibited by either cycloheximide or actinomycin D, as was shown previously for rat calvaria cell cultures. These results indicated the presence of a functional domain of PTH in the central part of the molecule which exerts its mitogenic-related effects on osteoblast- and chondroblast-like cells in a cyclic AMP-independent manner. Since cyclic AMP formation by PTH leads to bone resorption, specific mid-region fragments of PTH might prove suitable for use in vivo to induce bone formation without concomitant resorption.

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