Induction of cytolysis of cultured lymphoma cells by adenosine 3':5'-cyclic monophosphate and the isolation of resistant variants.
Cultured mouse lymphosarcoma cells are killed on exposure to 0.1 mM N(6),O(2')-dibutyryl-adenosine 3':5'-cyclic monophosphate. A population of cells resistant to the killing effect of dibutyryl cyclic AMP at concentrations as high as 1 mM was selected. The growth characteristics of the resistant cells were similar to those of the sensitive parental line. However, the resistant cells contain less cytoplasmic cyclic AMP-binding proteins and decreased cyclic AMP-stimulated protein kinase activity. It is proposed that transition from sensitivity to resistance to dibutyryl cyclic AMP in lymphoma cells is connected with a modification of the cyclic AMP-binding protein, which appears to be the regulatory subunit of the cyclic AMP-activated protein kinase.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002474:Cell-Free System; D002478:Cells, Cultured; D002852:Chromatography, Ion Exchange; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D008223:Lymphoma / Q000201:enzymology; D051379:Mice; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000378:metabolism; D010770:Phosphotransferases / Q000302:isolation & purification / Q000378:metabolism; D011485:Protein Binding; D011955:Receptors, Drug; D014316:Tritium
D009363:Neoplasm Proteins; D011955:Receptors, Drug; D014316:Tritium; D000242:Cyclic AMP; D010770:Phosphotransferases