Patterns of cyclic nucleotides and related enzymes in normal and gross-virus-transformed rat thymocytes

Abstract

Cyclic nucleotide (cAMP and cGMP) intracellular levels and cyclase and phosphodiesterase activities were determined in normal and Gross-virus-transformed thymocytes. Many changes in cyclic nucleotide levels and in cyclase activities were observed, but the differences are difficult to evaluate since the changes clearly depend on how the data are expressed: cell number, protein content or DNA content. However, the cAMP cGMP molar ratio was significantly lower in transformed than in normal thymocytes, thus indicating that a relative prevalence of cGMP over cAMP was present in these cells. Transformed thymocytes were sensitive to the stimulating effect of azide and theophylline, but, at variance with normal cells, did not respond to serotonin, carbamylcholine or d,l-isoproterenol. Preincubation with theophylline allowed a cAMP response to d,l-isoproterenol, but no cGMP response to serotonin or carbamylcholine was found. Alterations in the subcellular distribution of guanylate cyclase were also found in transformed thymocytes, as suggested by the relative increase in the particulate enzyme activity of these cells. Both cAMP and cGMP phosphodiesterase activities were significantly higher in transformed than in normal thymocytes. These data are in agreement with the hypothesis that cyclic nucleotide metabolism is abnormal in malignancy.