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Stimulation of the Synthesis of Mouse Epidermal Histones by Tumor-promoting Agents¹

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

Topical application of 17 nmoles of the potent tumor promoter, 12-O-tetradecanoylphorbol-13-acetate, resulted in a stimulation of the incorporation of [³H]lysine into epidermal histones. Maximum incorporation occurred 24 hr after treatment, concurrent with maximum DNA synthesis. The effects of phorbol and two phorbol esters on histone synthesis were related to their tumor-promoting activities.

Treatment with hydroxyurea partially prevented the phorbol ester-induced stimulation of both DNA and histone synthesis, although it had no effect on the stimulation of protein synthesis. These findings are consistent with the likelihood that phorbol ester-induced epidermal histone synthesis is the result of a coupling between DNA synthesis and histone synthesis.

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: Frederick Cancer Research Center, Frederick, Md. 21701.

Received 7/ 5/77. Accepted 9/20/77.