Cell population kinetics in hairless mouse epidermis following a single topical application of 12-O-tetradecanoylphorbol-13-acetate II.

It is known that a single application of 17 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) to hairless mouse skin first induces (from 0-12 h) a short block in mitotic activity followed by a transient stimulation of proliferation (from 12-96 h) characterized by multiple waves of rapid proliferation in partly synchronized basal cells, leading to hyperplasia. The replication rate of basal cells, the number of basal and suprabasal (maturing) cells per unit of interfollicular epidermis and the number of squamous layers in the stratum corneum were recorded. Changes in the nuclear area of living cells were monitored by morphometry. The changes in the rate of basal cell proliferation are accompanied by concomitant waves of increased rates of cell maturation and cell loss, with a considerable reduction in epidermal cell transit time. When 14-15 squamous layers were observed, this resulted in an increased cell loss, which was visible as scaling from 24 h onwards. The total cell mass lost from 16 to 72 h after TPA application amounted to about 67% of the newborn cell mass. Thus the hyperplasia occurring after a single TPA treatment results from a considerably enhanced cell proliferation that exceeds concomitant increases in the rates of cell maturation and loss. There is no delayed maturation. The results are also consistent with the chalone theory of epidermal growth regulation, assuming that the G1 chalone is produced during cell maturation.