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Late Ultrastructural Changes Induced by 12-O-Tetradecanoyl-phorbol-13-acetate in Mouse Epidermis and Their Reversal¹

Department of Pathology, University of Toronto, 100 College Street, Toronto, Ontario, M5G 1L5, Canada

The ultrastructural changes induced in mouse interfollicular epidermis (IFE) up to 4 weeks after a single application of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) are described. The increase in the thickness, number of nucleated cell layers, and mitotic index of IFE reverts to control levels 120 hr after treatment. The ultrastructural changes induced by TPA in the epidermal cells are considerably reduced in most areas of the IFE by 120 hr, and by 2 weeks after treatment, the fine structural characteristics of most basal cells are similar to those of normal or acetone-treated control IFE.

The reversal of the changes induced by TPA is not uniform. At 120 and 144 hr, foci of hyperplasia persist and sometimes have fine structural characteristics that are distinct from those of other epidermal cells. Similar phenotypically altered cells are occasionally found isolated 2 weeks after TPA treatment, but by 4 weeks they are not longer observed, indicating that the alterations induced by TPA in these cells are reversible. The peculiarity of their ultrastructural characteristics, the presence of mitoses in them, and their absence in normal or acetone-treated IFE suggest that these cells are variants of the cell population induced by TPA or are made to express this phenotypic characteristic by TPA.

¹ This work was supported by Grant-in-Aid MA-4340 of the Medical Research Council of Canada.

Received 12/15/72. Accepted 2/12/73.