THE NATURE OF THE EPIDERMAL GROWTH PRODUCED BY THE 1ST APPLICATION OF 12-0-TETRADECANOYL-PHORBOL-13-ACETATE ON THE SKIN OF MICE INITIATED WITH DIMETHYLBENZANTHRACENE

[摘要] The kinetics of epidermal growth following a single application of 17 nmol of [the tumor promoter] 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in the back skin of CD-1 female mice initiated with 200 nmol dimethylbenzanthracene (DBMA) were studied to investigate skin chemical carcinogenesis. Within 5 h after the application of TPA there was an increase in epidermal wet weight and total protein (protein per unit area of epidermis) which reached a peak of 3-4 times that of normal in 3-4 days. Total DNA began to increase more slowly than epidermal wet weight and total protein but reached its peak of about 2 times normal by day 2. These parameters remained elevated until 7 days after TPA treatment when they began to return toward normal levels. By day 10, the end of the experimental period, levels were still significantly elevated above normal. Within 3 h after TPA application, a slight hyperplasia was evidenced by small increases in the number of nucleated cells layers, the total number of epidermal nuclei per millimeter interfollicular epidermis (IFE) and the number of suprabasal nuclei per millimeter IFE. This modest hyperplasia was lost by 8 h and followed by principal hyperplasia which peaked by day 2 at about 2 times normal. During hyperplasia there was considerable epidermal cell damage as evidenced by cytoplasmic vacuolization, nuclear pyknosis and the separation of the epidermis from the dermis. The number of basal nuclei per millimeter IFE decreased. A small increase in mitotic activity of the basal epidermal cells was seen at 3 h at the time the transient hyperplasia occurred. Mitotic activity decreased to below normal levels by 5 h and then increased with principle hyperplasia with a peak at day 1. The overall growth produced by the 1st application of TPA in initiated mouse skin was of greater duration than that produced by TPA in normal mouse skin.