This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mufson, R. A. Articles by Boutwell, R. K. Search for Related Content PubMed PubMed Citation Articles by Mufson, R. A. Articles by Boutwell, R. K.

The Effect of the Phorbol Ester Tumor Promoters on the Basal and Catecholamine-stimulated Levels of Cyclic Adenosine 3':5'-Monophosphate in Mouse Skin and Epidermis in Vivo¹

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

To measure the in vivo levels of cyclic adenosine 3':5'-monophosphate (cyclic AMP) in mouse skin, precautions must be taken to avoid artifactual alterations after excision of the skin from the mouse. With such precautions, the level of cyclic AMP in mouse epidermal-dermal preparations was unchanged 1 to 18 hr after application of 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse skin. The accumulation of cyclic AMP in response to isoproterenol or the naturally occurring catecholamine epinephrine was, however, significantly diminished 9 to 24 hr after application of TPA. No enhanced accumulation of cyclic AMP in response to -adrenergic stimulation accompanied this diminished ß-adrenergic responsiveness. Experiments with pure epidermis confirmed that these observations reflected the effects of TPA on the epidermal cells in the epidermaldermal preparations. The metabolism of isoproterenol in TPA-treated epidermis was the same as that in control epidermis.

Finally, the tumor-promoting activity of various doses of TPA and of other phorbol esters correlated with their ability to diminish the ß-adrenergic responsiveness of the epidermis.

¹ This work was supported by Grants CA-07175, T32-CA09020, and CA-5002 from the National Cancer Institute.

² Recipient of National Cancer Institute Post Doctoral Fellowship F22 CA 00586-01.

Received 7/26/76. Accepted 12/ 6/76.

This article has been cited by other articles:

				T.J. Slaga, S.M. Fischer, L.L. Triplett, and S. Nesnow Comparison of Complete Carcinogenesis and Tumor Initiation and Promotion in Mouse Skin: The Induction of Papillomas by Tumor Initiation-Promotion a Reliable Short Term Assay International Journal of Toxicology, January 1, 1982; 1(1): 83 - 99. [Abstract] [PDF]