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

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

A single topical application of 0.017 µmole of the potent tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate, resulted in a stimulation of the phosphorylation of mouse epidermal histones with an early peak at 2 hr followed by peaks between 1 and 3 days after treatment. The effect of phorbol and two phorbol esters on histone phosphorylation was found to be related to their tumor-promoting activity as well as to their capacity to stimulate RNA and DNA synthesis. Stimulation of histone phosphorylation was slight following treatment with the weak promoter, phorbol-12,-13-dibenzoate, and nonexistent after treatment with phorbol, which has no tumor-promoting activity. A dose dependency relationship was established linking the ability of 12-O-tetradecanoyl-phorbol-13-acetate to stimulate histone phosphorylation with its ability to promote tumors.

Cycloheximide prevented the increase in histone phosphorylation caused by 12-O-tetradecanoyl-phorbol-13-acetate but had no effect on histone phosphorylation in control mice.

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.

Received 5/31/72. Accepted 10/11/72.