Inhibition of the effects of 12-O-tetradecanoylphorbol-13-acetate on mouse epidermal glutathione peroxidase and ornithine decarboxylase activities by glutathione level-raising agents and selenium-containing compounds.

Abstract

The present study was undertaken to determine the effect of 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent tumor promoter known to inhibit superoxide dismutase (SOD) (superoxide: superoxide oxidoreductase, EC 1.15.1.1) and catalase (CAT) (H2O2: H2O2 oxidoreductase, EC 1.11.1.6) activities, on mouse epidermal glutathione (GSH) peroxidase (glutathione: H2O2 oxidoreductase, EC 1.11.1.9) activity in vivo and in vitro. TPA led to a rapid and transient increase in GSH peroxidase specific activity within 30 min followed by a decrease from 1 to 12 h. Incubation of isolated epidermal cells with GSH level-raising agents and/or selenium-containing compounds increased remarkably basal GSH peroxidase activity, and thus, abolished totally the prolonged inhibitory effects of TPA on this enzyme. The inhibitory effects of 0.2 mM cysteine (Cys) or 0.5 mM GSH and 2.5 microM Na2 SeO3 or 50 microM selenocystamine on TPA-decreased GSH peroxidase activity were additive, in relation with their additive inhibitory effects on TPA-induced ornithine decarboxylase (ODC) (L-ornithine carboxylase, EC 4.1.1.17) activity. These data support the hypothesis that the stimulators of the GSH-dependent antioxidant protective system of the epidermal cells may inhibit the oxidative challenge linked to skin tumor promotion by TPA.