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Interactions of Phorbol Esters with Cellular Membranes in Vitro¹

Division of Neurosurgery and McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, Wisconsin 53706

Esters of phorbol, a family of tumor-promoting agents, interact in vitro with cellular membranes. In CsCl equilibrium density gradients, isotopically labeled phorbol didecanoate cosediments with microsomal and nuclear membranes prepared from rat liver. The interaction between these membranes and the promoting compound is enhanced in the presence of native or denatured DNA. Moreover, changes in membrane density and in the amounts of radioactive DNA associated in vitro with the membrane are seen in CsCl in the presence of several unlabeled phorbol esters. The possibility that alterations of cellular membranes are related to tumor promotion is considered.

¹ This work was supported by National Cancer Institute Grants CA-07175 and CA-08959.

Received 2/22/73. Accepted 8/23/73.