Abstract

Reduced/oxidized glutathione (GSH/GSSG) and the activities of catalase (CAT), Superoxide dismutase (SOD), glutathione peroxidase (GPX) and xanthine oxidase (XO) were quantitated in initiated SENCAR mice being promoted with 1 μg of 12-O-tetradecanoylphorbol-13-acetate (TPA). Within 24 hr of 4 or 10 applications of TPA epidermal SOD, CAT, GPX and XO specific activities were∼56, 39, 76 and 350% of the values measured in solvent-treated mice. SOD, CAT and XO activities in papillomas and squamous cell carcinomas (SCC) were∼15%, 30% and 175% respectively, of the activities in skins of age-matched, control mice. GPX activities were unaffected in papillomas but reduced 22% in SCC. Total epidermal GSHt (GSH+GSSG) and GSSG contents (nmol/g tissue) were not significantly altered 0.5, 4 or 24 hr after 1 or 4 applications of TPA. These studies suggest (a) that TPA orchestrates changes in enzymes involved in reactive oxygen metabolism to levels characteristic of the skin tumor phenotype; and (b) if TPA induces oxidative stress in vivo in murine epidermis, it cannot be detected by measurements of GSH and GSSG.

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