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

Journal Article · Thu Sep 01 00:00:00 EDT 1977 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.74.9.3908· OSTI ID:7091527

Lichti, U ^[1]; Slaga, T J; Ben, T; Patterson, E; Hennings, H; Yuspa, S H

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1. National Cancer Inst., Bethesda, MD

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 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 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 prior to TPA, and its continued presence after TPA treatment is not required. Paradoxically, FA potentiates the increase in ornithine decarboxylase activity after TPA administration 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 suggest that FA exerts its antipromotion effect by reducing the sensitivity of the cell to polyamines or by reducing intracellular polyamine levels.

• OSTI ID: 7091527
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 74:9; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMALS
BIOSYNTHESIS
BODY
CELL PROLIFERATION
DECARBOXYLASE
DISEASES
DNA
DRUGS
ENZYMES
EPIDERMIS
EPITHELIUM
IN VITRO
IN VIVO
LYASES
MAMMALS
METABOLISM
MICE
NEOPLASMS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
RODENTS
SKIN
SYNTHESIS
TISSUES
VERTEBRATES