Comparison of differentiation patterns in 12-O-tetradecanoylphorbol-13-acetate-treated epidermis and fetal epidermis

12-O-Tetradecanoylphorbol-13-acetate (TPA)-treated adult epidermis as well as untreated fetal and adult epidermis were investigated to elucidate the effect of TPA in terms of cell differentiation using techniques of ultrastructural stereology. Twenty-four hours after a single application of TPA, the treated epidermis was characterized by involutional changes, i.e., increased volume density of intercellular spaces and of mitochondria, vacuoles, and cytoplasmic ground substance in the basal layer. However, 48 h after application, the TPA-treated epidermis was very similar to fetal epidermis, i.e., high volume density of nuclei ribosomes, rough endoplasmic reticulum, membrane-coating granules, and keratohyalin granules, and low volume density of bundled filaments in the upper layers. These stereological data indicate that the changes observed 48 h after TPA treatment were related not only to increased cell proliferation but also to inhibition of cell differentiation expressed as a reversion of the adult differentiation patterns and the acquisition of fetal characteristics in all epidermal layers.