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Effects of 12-O-Tetradecanoylphorbol-13-acetate and Mezerein on Epidermal Ornithine Decarboxylase Activity, Isoproterenol-stimulated Levels of Cyclic Adenosine 3':5'-Monophosphate, and Induction of Mouse Skin Tumors in Vivo¹

Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830 [S. M. F., T. J. S., G. L. G.] and McArdle Laboratory for Cancer Research, University of Wisconsin Medical Center, Madison, Wisconsin 53706 [R. A. M., A. K. V., R. K. B.]

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate and the antileukemic agent mezerein are diterpene esters of plant origin with certain structural similarities. Both compounds, when applied topically to mouse skin, were equipotent on a molar basis in inducing hyperplasia, inflammation, and ornithine decarboxylase activity, as well as in reducing cyclic adenosine 3':5'-monophosphate accumulation in response to ß-adrenergic stimulation. In contrast, mezerein was much less effective as a tumor promoter; the phorbol ester at 8.5 nmol/application yielded 78-fold more tumors than did 8.5 nmol mezerein per application to similarly initiated SENCAR mice. The superiority of the phorbol ester was nearly as great in CD-1 mice.

These results suggest that although the induction of hyperplasia and ornithine decarboxylase activity may be necessary components of the carcinogenic process, they are not sufficient; 12-O-tetradecanoylphorbol-13-acetate must accomplish an essential event not accomplished by mezerein.

¹ Research jointly sponsored by the NIH under Grant CA 07175; the National Cancer Institute under Contract YO1CP70227; and the Office of Health and Environmental Research, United States Department of Energy, under Contract W-7405-eng-26 with the Union Carbide Corporation.

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

³ To whom requests for reprints shluld be addressed.

Received 7/ 9/79. Accepted 8/29/79.

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