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Effects of retinoids on phorbol ester-stimulated epidermal DNA synthesis and hyperplasia in hairless mice.

Abstract
We investigated the effects of the retinoids, all-trans retinoic acid (t-RA), 13-cis retinoic acid, etretinate, and arotinoid ethyl ester, on 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced DNA synthesis, and epidermal hyperplasia in hairless mouse skin. Topical application of these retinoids produced dose-dependent inhibition of the TPA-induced epidermal DNA synthesis as measured by [3H]thymidine incorporation at 15 h after TPA application. However, this inhibition was only transient and did not affect the corresponding increase in epidermal cell layers measured at 40 or 70 h after TPA application. Fluocinonide also inhibited the epidermal DNA synthesis and failed to block TPA-induced epidermal hyperplasia. However, fluocinonide did effectively suppress the inflammation caused by TPA. In this paper we have shown that the suppression of TPA-stimulated DNA synthesis is a general property of topically applied retinoids. The biologic significance of a temporary suppression of TPA-stimulated epidermal DNA synthesis by the retinoids and fluocinonide is not understood at this time.
AuthorsG J Gendimenico, X Nair, P L Bouquin, K M Tramposch
JournalThe Journal of investigative dermatology (J Invest Dermatol) Vol. 93 Issue 3 Pg. 363-7 (Sep 1989) ISSN: 0022-202X [Print] United States
PMID2768837 (Publication Type: Journal Article)
Chemical References
  • Retinoids
  • Fluocinonide
  • DNA
  • Tetradecanoylphorbol Acetate
Topics
  • Animals
  • DNA (biosynthesis)
  • Dose-Response Relationship, Drug
  • Epidermis (drug effects, metabolism, pathology)
  • Female
  • Fluocinonide (pharmacology)
  • Hyperplasia
  • Mice
  • Mice, Hairless
  • Retinoids (pharmacology)
  • Stimulation, Chemical
  • Tetradecanoylphorbol Acetate (pharmacology)

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