Effects of retinoids on phorbol ester-stimulated epidermal DNA synthesis and hyperplasia in hairless mice.
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.
Bristol-Myers Co., Pharmaceutical Research and Development Division, Buffalo, New York 14213.
G J
GJ
Gendimenico
X
X
Nair
P L
PL
Bouquin
K M
KM
Tramposch
D000818:Animals; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005447:Fluocinonide / Q000494:pharmacology; D006965:Hyperplasia; D051379:Mice; D008812:Mice, Hairless; D012176:Retinoids / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D012176:Retinoids; D005447:Fluocinonide; D004247:DNA; D013755:Tetradecanoylphorbol Acetate