Evaluation of epidermal cell kinetics following freezing or wounding of mouse skin and their potential as initiators of carcinogenesis.

It has been shown that abrasion, and consequent regenerative hyperplasia, acts as a promoting agent in mouse skin carcinogenesis. The present experiments were designed to evaluate the possibility that ulceration and its consequent regeneration might also act as initiators. Female Sencar mice were used, and ulceration was induced either by the application of a frozen rod or by incision of the skin of the back. The time course of the ulceration, regeneration, and repair of the mouse skin following ulceration by either method was evaluated utilizing morphologic and autoradiographic techniques. The labeling index of the epidermis, using [3H]-thymidine and autoradiography, reached a maximum level 7 days after ulceration and the epidermal hyperplasia was most pronounced at days 7-14. The potential initiating activity of freeze ulceration or incision was evaluated by performing these procedures on 7-week-old female Sencar mice followed by promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA) applied twice a week to the ulcerated areas, 5.2 micrograms in each application. Extending the total experimental observation to 1 year indicated that freeze ulceration and incision did not initiate carcinogenesis in the mouse skin when promoted with TPA.