Adenosine 3', 5'-monophosphate (cyclic 3', 5'-AMP) and other cyclic nucleotides play an essential role in regulating basic biological processes, and there is increasing evidence suggesting their involvement in the etiology of several disease states including cancer. The general objective of the proposed research program is to find pharmacologic agents which can selectively alter the concentration of cyclic 3', 5'-AMP or other cyclic nucleotides in specific organs and discrete cell types. More specifically, we hope to control the growth of cancer cells by altering their cyclic nucleotide level with agents which are specific and selective for the malignancy. To this end, our immediate goal is to isolate and characterize the various forms of phosphodiesterase in normal cells and in different types of cancer cells. Once we have established the type and distribution of phosphodiesterase in these cells, we will search for compounds that will selectively inhibit the form of the enzyme which predominates in the cancer cells. We will then measure the level of cyclic 3', 5'-AMP in these cells and in normal tissues in vivo and in vitro after administering the specific phosphodiesterase inhibitors. Ideally, the concentration of cyclic 3'. 5'-AMP should increase only in the cancer cells, leaving the normal cells unaffected. Finally, in order to determine whether these results have any clinical significance, we will administer the inhibitor to animals with various forms of cancer to determine whether the course of the malignancy can be altered without affecting the normal function of the animal.