Gendimenico G J, Nair X, Bouquin P L, Tramposch K M
Bristol-Myers Co., Pharmaceutical Research and Development Division, Buffalo, New York 14213.
J Invest Dermatol. 1989 Sep;93(3):363-7.
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.
我们研究了维甲酸类物质，即全反式维甲酸（t-RA）、13-顺式维甲酸、依曲替酯和芳维甲酸乙酯，对12-O-十四烷酰佛波醇-13-乙酸酯（TPA）诱导的无毛小鼠皮肤DNA合成及表皮增生的影响。在涂抹TPA后15小时，通过[3H]胸腺嘧啶核苷掺入法测定，局部应用这些维甲酸类物质可产生剂量依赖性地抑制TPA诱导的表皮DNA合成。然而，这种抑制只是短暂的，并不影响在涂抹TPA后40或70小时所测得的表皮细胞层数的相应增加。氟轻松也抑制表皮DNA合成，且未能阻止TPA诱导的表皮增生。然而，氟轻松确实有效地抑制了TPA引起的炎症。在本文中，我们已表明局部应用维甲酸类物质抑制TPA刺激的DNA合成是其普遍特性。目前尚不清楚维甲酸类物质和氟轻松对TPA刺激的表皮DNA合成的暂时抑制的生物学意义。
