[Epigenetic mechanism of tumor promotion. Interrelationship between inflammation and ornithine decarboxylase activity induced in vitro by the carcinogenic 12-O-tetradecanoyl-phorbol-13-acetate].
Topical application of 2 micrograms 12-O-tetradecanoyl-phorbol-13-acetate (TPA) regularly induced two early events in mouse skin: inflammatory reaction localized in dermal compartment and stimulation of ornithine decarboxylase activity in epidermal cells, in relation to polyamine synthesis and cell division. These reactions were followed, after 48 hrs. by an epidermal hyperplasia. At this stage, another TPA treatment induced a strong ODC activity concurrent with severe inflammation of the dermis. Inhibition of the synthesis of inflammatory factors may antagonize TPA-induced ODC, but the protective potencies differs according to the evolutive stages of the cell. After the first TPA treatment the anti-inflammatory compounds dexamethasone and indomethacin effectively inhibited ODC activity. In contrast during the proliferative stage epidermal cell function may be less dependent on inflammatory factors; thus only partial protection was observed with the inflammatory inhibitors.
D000818:Animals; D003907:Dexamethasone / Q000627:therapeutic use; D004817:Epidermis / Q000201:enzymology; D005260:Female; D006965:Hyperplasia / Q000139:chemically induced; D007213:Indomethacin / Q000627:therapeutic use; D007249:Inflammation / Q000139:chemically induced* / Q000188:drug therapy / Q000201:enzymology; D051379:Mice; D008815:Mice, Inbred Strains; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D012871:Skin Diseases / Q000139:chemically induced* / Q000201:enzymology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D003907:Dexamethasone; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin
Mécanisme épigénétique de la promotion tumorale. Interrelation entre l'inflammation et l'activité d'ornithine décarboxylase induites in vitro par le cancérogène 12-O-tetradecanoyl-phorbol-13-acetate.