A morphometric study of dedifferentiated and involutional dark keratinocytes in 12-O-tetradecanoylphorbol-13-acetate-treated mouse epidermis.

The epidermis of mice treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) was investigated using the method of stereological cytology. These procedures were carried out in order to quantify the morphological changes taking place in basal cells, the presumed target cells of TPA in the epidermis. The basal layer of the treated epidermis was composed of TPA-induced dark basal keratinocytes (DC) and clear basal keratinocytes. TPA-induced DC could be divided into two types. Type 1 was characterized by a relatively high volume fraction of ribosome and nonbundled filaments and by a low volume fraction of bundled filaments. These characteristics of type 1 DC were relatively constant over the observation period. Type II DC were characterized by a high volume density of mitochrondria , bundled filaments, and cytoplasmic vacuoles. This type of DC was seldom seen in normal epidermis but constituted approximately 20% of the dark cells in the epidermis 24 and 48 hr after treatment with TPA. In contrast, clear basal keratinocytes exhibited time-dependent changes such as an increase of the relative volume of nuclei; an increase in the volume density of mitochondria, nonbundled filaments, and ribosomes; and a decrease in the volume density of bundled filaments. Both the qualitative and quantitative analyses of TPA-treated and fetal epidermis suggest a close similarity between type 1 DC and DC seen in normal fetal epidermis, thus supporting the view that type 1 DC are poorly differentiated cells or dedifferentiated cells, different from type II or involutional DC.