Epidermal cell cycle and transit times during hyperplastic growth induced by abrasion or treatment with 12-O-tetradecanoylphorbol-13-acetate.

The purpose of this investigation was to determine the cellular kinetics of the epidermis during hyperplastic growth in CD-1 mice induced by treatments effective in skin tumor promotion: abra sion or the application of 12-O-tetradecanoylphorbol-13-acetate (TPA). Following removal by abrasion, the epidermis regenerated from intrafollicular epidermal cells. The maximal increase in the number of epidermal cells, over 2-fold from normal, was reached by 4 days after abrasion. Regression of the hyperplasia began about Day 7 and continued through Day 20, resulting in a nearly normal epidermis. The growth fraction measured at 3 days after abrasion did not change from its normal value of about 100%. However, the cell cycle time of basal keratinocytes 3 days after abrasion was drastically reduced to about 11 hr compared to 5 to 7 days in normal epidermis. The cell cycle time gradually increased to 14 hr at 5 days, 1 to 2 days at 7 days, and 4 to 5 days at 14 days after abrasion. The reduction in the length of the cell cycle time was primarily due to a decrease in the length of Gì.The rate of epidermal cell loss was measured by the epidermal transit time, the time required for [3H]thymidine-labeled basal cells to reach the uppermost nucleated layer. Labeled nuclei were followed through the epidermal columns, when pres ent. Transit time was dramatically reduced from 8 days in normal skin to 1 day by 3 days following abrasion, then rose to 2 days by 5 days postabrasion, 4 days by 7 days postabrasion, and by 6 days 14 days postabrasion. A single application of 17 nmol of TPA resulted, within 1 day, in over a 50% increase in the total number of epidermal cells. This thickness was maintained until about Day 4, and then regression began resulting in an essentially normal epidermis by 10 days. As after abrasion, the growth fraction 3 days after treatment with TPA was about 100%, that is, not changed from normal. The cell cycle time, however, was again dramatically reduced to 16 hr beginning at 1 hr, 25 hr at 3 days, 2 to 3 days at 5 days, and 3 to 5 days at 10 days after application of TPA. Also, as after abrasion-induced hyperplasia, the transit time was reduced to 2 days at 1 hr, 4 days at 3 days, and 5 days at 5 and 10 days following treatment with TPA. The decrease in the cell cycle time can be accounted for by the decrease in the length of G,. The results of this investigation demonstrate that the produc tion of an epidermal hyperplasia following abrasion or the appli cation of 17 nmol of TPA is associated with both an increase in 1This work supported by NIH Grants AM 18219 and AG 01324. 2Work performed in partial fulfillment of the requirements for the Ph.D. in biology in the Graduate School of Syracuse University, Syracuse, N. Y. Present address: The University of Texas System Cancer Center, Science Park Research Division, P. O. Box 389, Smithville, Texas 78957. 3To whom requests for reprints should be addressed. Received March 10,1983; accepted July 12,1983. cell proliferation and cell loss. The increased cell proliferation can be accounted for by the decrease in the length of the cell cycle. It appears that the increase in epidermal cell loss may be also linked to the decrease in the length of the cell cycle, since all suprabasal cells arise from the basal cells.