Short Communication Incorporation of H-Thymidine into DNA: Inhibition by Dithranol and its Di- and Triacetate

Dithranol was introduced into anti-psoriatic therapy in 1916, but the principle of its activity remains unkown with regard to the quantitative aspects of its efficacy e.g. in enzyme inhibition, D N A interaction and interference with lipid metabolism. In vitro experiments have indicated that dithranol irreversibly inhibits glucose-6-phosphate-dehydrogenase (EC 1.1.1.49) [10] and the incorporation of thymidine into D N A [6]. Compared with dithranol, there have been few investigations of dithranol triacetate and dithranol diacetate; dithranol triacetate has been introduced as an anti-psoriatic (Exolan) [5]). In vitro experiments using dithranol triacetate and dithranol diacetate with human serum have revealed that both molecules are hydrolytically and oxidatively degraded [12]. The different rates of absorption of differently labelled moieties of dithranol triacetate ( 1 4 C H 3 C O , ^ a n thracene) have been explained by (partial) hydrolysis in or on the skin [13], which suggests that this compound has a pro-drug character. On the other hand, both dithranol acetates inhibit glucose-6-phosphatedehydrogenase [9]. In order to obtain a better comparison between dithranol and its acetates, we determined the influence of these compounds on the incorporation of thymidine into epidermal D N A . Dithranol and its triand diacetate were prepared as has previously been described [12]; dithranol and its triacetate were dissolved in acetone, and dithranol diacetate was dissolved in C H 2 C 1 2 (for concentrations, see Fig . 2). For each concentration (Fig. 2), five female mice (Charles River Wiga; 25 — 30 g) were shaved on OH 0 OH OAc OAc OAc OAc 0 OAc