Local anesthetics inhibit induction of ornithine decarboxylase by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate.

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Abstract
The induction of ornithine decarboxylase (L-ornithine carboxy-lyase) activity in mouse epidermal cells in vivo and in vitro occurs rapidly after exposure to the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). This induction has characteristics of a cell surface receptor-mediated process. Local anesthetics modify a variety of cellular responses mediated by membrane receptors. When cultured mouse epidermal cells were exposed to the local anesthetics lidocaine, tetracaine or procaine (0.1-1 mM), induction of the decarboxylase by TPA was inhibited by > 90%. In vivo, lidocaine essentially abolishes the decarboxylase response of mouse epidermis when applied shortly after TPA. Local anesthetics have no effect on the enzyme''s activity when added directly to the assay mixture and, in concert with TPA, have only a minimal effect on overall protein synthesis. Lidocaine has no effect on TPA-stimulated DNA synthesis in vitro (12-fold with or without lidocaine). Local anesthetics also markedly inhibit induction of the decarboxylase by UV light, which is probably not membrane mediated. In culture, lidocaine has only a small inhibitory effect on ornithine decarboxylase when given before TPA but is an effective inhibitor even when given up to 4-5 h after the promoter, a time when decarboxylase activity has already increased. Local anesthetics, which are tertiary amines apparently do not act at the site of interaction of TPA and its putative receptor but may be acting specifically on polyamine biosynthesis. These drugs could be useful agents to determine the role of the polyamine pathway in tumor promotion.