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Phorbol-12-myristate-13-acetate Effect on Cyclic Adenosine 3',5'-Monophosphate Levels in Mouse Skin and Inhibition of Phorbol-myristate-acetate-promoted Tumorigenesis by Theophylline¹

Department of Environmental Medicine, New York University Medical Center, New York, New York 10016

The most effective tumor-promoting agent, phorbol-myristate-acetate, lowers cyclic adenosine 3'5'-monophosphate levels in mouse skin. A decrease is seen 1 hr after treatment; at 2 hr, a minimum is reached and maintained for 24 hr. At 48 hr, the cyclic adenosine 3',5'-monophosphate level rises to control or greater values. Theophylline inhibits phorbol-myristate-acetate-promoted tumorigenesis. It appears that a decrease in cyclic adenosine 3',5'-monophosphate levels is related to tumor promotion.

¹ This investigation was supported by project grants from the NIH (USPHS Research Grants ES-00505 and CA-08621) and a grant from the Allied Chemical Corporation and is part of a Center Program by the National Institute of Environmental Health Sciences Grant ES-00260. This work was previously reported (4).

Received 3/ 2/74. Accepted 8/27/74.

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