EFFECT OF ZINC PYRITHIONE ON SKIN CELLS 9 effects on DNA synthesis which, as suggested by the experiments with sodium pyrithione, are attributable to their pyrithione moieties. Thus, pyrithione is, except for its ring structure, very similar to hydroxy-2-thiourea which also exhibits DNA synthesis inhibition. Additionally, it has been shown that all of the hydroxyurea related compounds which form complexes with metal ions inhibit synthesis of DNA in a HeLa cell system (11). l0 v 1 05 ß Control ß 0.04 jtg/ml [] 0.08 • 0.12 ZPT o 0.20 Cultu re Day Figure 6a. See legend on following page. } ,

10 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS 1 0 7 I 0 6 1 o 5 I I o 5 Cultu re Day Figure 6b. Effect of ZPT on the growth of JTC-17 cells seeded in different concentrations. A: Cells were initially cultured at a 3.0 x 10 4 cell density with simultaneous addition of ZPT at indicated concentrations. B: Cells were initially cultured at a 3.2 x 10 5 cell density with simultaneous addition of ZPT at indicated concentrations. Arrow represents the time of the addition of drugs. Since actual inhibition of DNA synthesis by ZPT requires penetration of ZPT into epidermis as well as sequential contact with epidermal basal cells, whether or not the suppression of dandruff by ZPT could reasonably be interpreted in the terms of the inhibition of DNA synthesis observed here, remains to be established not only with regard to ZPT's permeability into the scalp skin but also for its actual in vivo cellular metabolic action. Our previous microbial study (1) has suggested that of greater significance for induction of clinical effectiveness is the factor of penetration of ZPT into the skin. This observation is based on the fact that the presence of ZPT molecules on scalp in concentrations capable of maintaining the continuous suppression of P. ovale does not necessarily result in reduction of dandruff. In a biological estimation of actually adsorbed ZPT molecules by in vitro minimum inhibitory concentration (MIC) values for its anti-yeast action, there seems to be at least 10 ppm of ZPT present within the upper layers of the scalp (1). Furthermore, surfactants used as main constituents of antidandruff shampoos because of their enhanced surface activities may accelerate percutaneous absorption (12). There is some evidence that dandruff scalp has a