The Effect of Dibutyryl Cyclic Adenosine Monophosphate on Synthesis of Sulfated Acid Mucopolysaccharides by Transformed Fibroblasts

The effect of dibutyryl-cyclic adenosine 3',5'-monophosphate and theophylline on the incorporation of [35S]sulfate into acid mucopolysaccharides by 3T3 and SV3T3 fibroblasts has been studied. SV40 transformation of 3T3 fibroblasts produced a marked decrease in the rate of synthesis of acid mucopolysaccharides, in agreement with the data of others. When the transformed cells were grown in medium supplemented with dibutyryl-cyclic AMP and theophylline for 3 days, they secreted, on the basis of cell protein, approximately 250% more labeled acid mucopolysaccharides during a 24-hour labeling period than did the nontreated controls. The secretion of a variety of sulfated acid mucopolysaccharides was increased including chondroitin-4- and -6-sulfate and dermatan sulfate. Comparison of the rate of sulfate incorporation into acid mucopolysaccharides and the rate of loss of previously labeled acid mucopolysaccharides from the cells indicated that the effect was due to a greater rate of synthesis of these compounds at the time of labeling rather than due to a decrease in the rate of their degradation.