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

The alterations in the cell population kinetics of mouse epidermis (hr/hr. Oslo strain) following a single topical application of 17 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) were studied using serveral methods simultaneously. During a period from 2-96 h following treatment, 452 mice were used to measure incorporation of tritiated thymidine into DNA (labeling index and specific activity), mitotic index, Colcemid arrested metaphase rates, and flow cytometric DNA measurements. The time course of the kinetic response to TPA could be divided into two different periods. Period I (0-12 h) was characterized by a temporary block of cells in S-phase and mitosis. In period II (12-96 h), partly synchronized cells displayed multiple waves of DNA synthesis and cell division, with a considerable reduction of the cell cycle time from 54 h down to 10-12 h. The resulting hyperplastic epidermis is therefore composed of a relatively high proportion of young, immature cells. Hence, some of the early biochemical alterations in mouse epidermis assumed to be specific for TPA as a tumor promotor, may merely be the result of a rapid population shift.