The difference between the effects of single and double applications of 12-O-tetradecanoylphorbol-13-acetate, a potent tumor promoter, on polyamine metabolism and nucleic acid synthesis in mouse epidermis

Double applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse skin at intervals of >48 h led to a larger induction of ornithine decarboxylase (ODC) and a smaller increase of DNA and RNA synthesis than did a single application. The largest induction of S-adenosylmethionine decarboxylase occurred at a 120 h interval between coupled TPA applications. The change in ODC activity was followed by a parallel change in putrescine level. At intervals <24 h, the first application of TPA appeared to induce a refractory state; the second application of TPA did not induce the polyamine biosynthetic enzymes nor cause an accumulation of polyamines. The effect of the second application of TPA on the synthesis of DNA and RNA was considerably less at all times than that of a single application.