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Effects of Phorbol and Four Diesters of Phorbol on the Incorporation of Tritiated Precursors into DNA, RNA, and Protein in Mouse Epidermis¹

McArdle Laboratory for Cancer Research, University of Wisconsin Medical Center, Madison, Wisconsin 53706

The effects of a single application of the same molar dose of phorbol and four phorbol diesters on precursor incorporation into mouse epidermal RNA, protein, and DNA at times up to 6 days after treatment were studied in skin tumor-susceptible mice. The potent tumor promoters, 12-O-tetradecanoyl-phorbol-13-acetate and phorbol-12,13-didecanoate, induced a prompt stimulation of incorporation of tritiated cytidine into RNA and of tritiated leucine into protein and, after a 12-hr lag period, the incorporation of tritiated thymidine into DNA was stimulated. In all cases, the increased incorporation into the macromolecular species was maintained for 2 to 4 days. Phorbol-12,13-dibenzoate, a weak promoter, stimulated the incorporation of precursors into these macromolecules in the same sequence, but for only 1 day. The very weak tumor promoters, phorbol and phorbol-12,13-diacetate, did not induce any detectable changes in tritiated precursor incorporation. The tumor-promoting ability of these phorbol esters correlates with their ability to induce a sustained stimulation of RNA, protein, and DNA synthesis in mouse epidermis.

¹ This work was supported in part by American Cancer Society Grant E-6M and by National Cancer Institute Grants CA-07175 and CA-05002.

² Present address: Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.

Received 3/22/71. Accepted 5/28/71.

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