Dexamethasone efficiently inhibits the promotion of tumors in mouse skin by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and reduces TPA-induced hyperplasia, as determined by histological examination and rate of incorporation of labeled precursors into macromolecules of mouse epidermis. When the protein complement of mouse epidermal cytosol was assayed by electrophoresis on acidic polyacrylamide gels, no significant effect of dexamethasone was found on rapid changes (3 hr) induced by TPA or on the protein complement of epidermis after 24 weeks of treatment. Dexamethasone effected a major reduction in a rapidly migrating protein fraction which was greately enhanced 48 hr after TPA treatment. An early enhancement of a more slowly moving protein fraction was not suppressed by dexamethasone, and this enhancement persisted to all time points investigated. These findings appear to be a direct demonstration that TPA has multiple effects on mouse skin, which can be separately affected by other influences. This is supportive evidence for the proposition that tumor promotion consists of two steps, conversion (of initiated cells to latent tumor cells) and propagation (of latent tumor cells to gross tumors).

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