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Increased Cyclic Adenosine 3':5'-Monophosphate Phosphodiesterase Activity in the Epidermis of Phorbol Ester-treated Mouse Skin and in Papillomas¹

McArdie Laboratory for Cancer Research, University of Wisconsin, Madison, Wisconsin 53706

The potent tumor promoter, 12-O-tetradecanoylphorbol-13-acetate, produced a 2- to 3-fold increase in the activity of both the low- and high-affinity forms of cyclic adenosine 3':5'-monophosphate phosphodiesterase activity 13 hr after application to mouse skin. The magnitude of the enzyme induction correlated with the tumor-promoting activity of several doses of 12-O-tetradecanoylphorbol-13-acetate and of other phorbol esters. The induction of the low-affinity phosphodiesterase could be blocked by prior i.p. injection of the microtubule poisons, colchicine and vinblastine. The low-affinity cyclic adenosine 3':5'-monophosphate phosphodiesterase activity of the epidermal component of mouse skin papillomas produced by two-stage tumorigenesis was 3 times that of the surrounding uninvolved epidermis.

¹ The work was supported by NIH Grants CA 07175 and CA 22484.

² Present address: Institute for Cancer Research, Columbia University College of Physicians and Surgeons, 701 W. 168th Street, New York, N. Y. 10032.

³ To whom requests for reprints should be addressed.

Received 9/25/78. Accepted 3/ 2/79.