title: Dissociation of tumor promoter-stimulated ornithine decarboxylase activity and DNA synthesis in mouse epidermis in vivo and in vitro by fluocinolone acetonide, a tumor-promotion inhibitor.
abstract: 12-O-Tetradecanoyl phorbol-13-acetate (TPA), a tumor promoter, stimulates DNA synthesis in mouse epidermal cells in vivo and in vitro. This response appears to be mediated through polyamine metabolism because ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17)activity is markedly increased shortly after promoter exposure and this induction varies in magnitude according to dose and promoter potency of a series of phorbol esters. In vitro, exogenous putrescine (0.01-10 mM) results in a dose-related increase and prolongation of promoter-stimulated DNA DNA synthesis, a phenomenon noted in other systems of polyamine-mediated growth stimulation. The anti-inflammatory steroid fluocinolone acetonide (FA), an inhibitor of tumor promotion, prevents TPA stimulation of epidermal proliferation in vivo and in vitro. In vitro, FA most effectively prevents stimulation of DNA synthesis when applied is not required. Paradoxially, FA potentiates the increase in ornithine decarboxylase activity after TPA administeration both in vivo and in vitro. Furthermore, the inhibition of TPA-stimulated DNA synthesis by FA in vitro can be reversed by exogenous putrescine. These results suggestthat FA exerts its antipromotion effect by reducing the sensitivity of the cell to polyamines or by reducing intracellular polyamine levels.
mesh_terms: D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D004261:DNA Replication / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005446:Fluocinolone Acetonide / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011700:Putrescine / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000378:metabolism*
chemical_list: D005446:Fluocinolone Acetonide; D004247:DNA; D002262:Carboxy-Lyases; D009955:Ornithine Decarboxylase; D011700:Putrescine
references.citation: Cancer. 1961 Nov-Dec;14:1306-15
references.pmid: 14008628
references.citation: J Cell Biol. 1976 Mar;68(3):512-20
references.pmid: 192729
references.citation: Proc Natl Acad Sci U S A. 1977 Feb;74(2):657-61
references.pmid: 191821
references.citation: Chem Biol Interact. 1977 Jun;17(3):331-47
references.pmid: 880700
references.citation: J Natl Cancer Inst. 1976 Nov;57(5):1145-9
references.pmid: 826651
references.citation: Cancer Res. 1976 Nov;36(11 Pt 1):4062-8
references.pmid: 975048
references.citation: Chem Biol Interact. 1974 Jun;8(6):379-94
references.pmid: 4846309
references.citation: Nat New Biol. 1972 Feb 23;235(60):247-9
references.pmid: 4502415
references.citation: Cancer Res. 1974 Jul;34(7):1577-80
references.pmid: 4365664
references.citation: Cell. 1974 Aug;2(4):229-33
references.pmid: 4369950
references.citation: Biochem Biophys Res Commun. 1972 Jan 31;46(2):605-9
references.pmid: 4333422
references.citation: Cancer Res. 1976 Jul;36(7 PT 2):2644-53
references.pmid: 1277170
references.citation: Annu Rev Biochem. 1976;45:285-306
references.pmid: 786151
references.citation: Cancer Res. 1975 Jul;35(7):1662-70
references.pmid: 48421
references.citation: J Biochem. 1975 Apr;77(4):879-93
references.pmid: 1150642
references.citation: Cancer Res. 1975 Sep;35(9):2426-33
references.pmid: 807325
references.citation: Nature. 1975 Jun 26;255(5511):733-4
references.pmid: 49027
references.citation: Med Biol. 1975 Jun;53(3):121-47
references.pmid: 169440
references.citation: J Natl Cancer Inst. 1974 Oct;53(4):1093-7
references.pmid: 4427390
references.citation: J Invest Dermatol. 1974 Oct;63(4):343-9
references.pmid: 4424714
references.citation: Z Krebsforsch Klin Onkol Cancer Res Clin Oncol. 1975 Nov 25;84(3):325-44
references.pmid: 128221
references.citation: Exp Cell Res. 1974 May;86(1):95-105
references.pmid: 4857507
references.citation: CRC Crit Rev Toxicol. 1974 Jan;2(4):419-43
references.pmid: 4822436
references.citation: Cancer Res. 1973 Mar;33(3):542-6
references.pmid: 4689903
references.citation: Cancer Res. 1972 Mar;32(3):450-4
references.pmid: 5061300
references.citation: J Invest Dermatol. 1976 Jul;67(1):199-208
references.pmid: 819592
references.citation: Clin Exp Immunol. 1976 Apr;24(1):54-62
references.pmid: 1084818
references.citation: Proc Natl Acad Sci U S A. 1976 May;73(5):1626-30
references.pmid: 1064034
references.citation: Proc Natl Acad Sci U S A. 1976 Jun;73(6):1858-62
references.pmid: 1064859
references.citation: Nature. 1976 Jul 29;262(5567):402-4
references.pmid: 958393
references.citation: Proc Natl Acad Sci U S A. 1975 Oct;72(10):4042-5
references.pmid: 1060087
references.citation: Science. 1976 Feb 13;191(4227):571-2
references.pmid: 1251193
references.citation: Cancer Res. 1975 Oct;35(10):2884-90
references.pmid: 1157054
references.citation: Chem Biol Interact. 1975 Sep;11(3):225-33
references.pmid: 1157191
references.citation: Biochemistry. 1975 Oct 7;14(20):4403-9
references.pmid: 1174509
references.citation: Exp Cell Res. 1975 Jan;90(1):8-14
references.pmid: 1168141