Effects of 12-O-tetradecanoylphorbol-13-acetate and mezerein on epidermal ornithine decarboxylase activity, isoproterenol-stimulated levels of cyclic adenosine 3':5'-monophosphate, and induction of mouse skin tumors in vivo.
The tumor promoter 12-O-tetradecanoylphorbol-13-acetate and the antileukemic agent mezerein are diterpene esters of plant origin with certain structural similarities. Both compounds, when applied topically to mouse skin, were equipotent on a molar basis in inducing hyperplasia, inflammation, and ornithine decarboxylase activity, as well as in reducing cyclic adenosine 3':5'-monophosphate accumulation in response to beta-adrenergic stimulation. In contrast, mezerein was much less effective as a tumor promoter; the phorbol ester at 8.5 nmol/application yielded 78-fold more tumors than did 8.5 nmol mezerein per application to similarly initiated SENCAR mice. The superiority of the phorbol ester was nearly as great in CD-1 mice.
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D003877:Dermatitis, Contact; D004224:Diterpenes; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D010212:Papilloma / Q000139:chemically induced*; D010703:Phorbol Esters / Q000633:toxicity*; D010704:Phorbols / Q000633:toxicity*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D010703:Phorbol Esters; D010704:Phorbols; C011309:mezerein; D000242:Cyclic AMP; D009955:Ornithine Decarboxylase; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate