The purpose of this investigation was to characterize the [3H]thymidine label-retaining and the 'maturing' classes of basal cells from the dorsal epidermis of adult SENCAR mice and to compare their early cellular kinetic responses to topical application of the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Autoradiography of epidermal whole mounts and cross sections demonstrated that injection of [3H]thymidine every 6 h for 1 week labeled 95% of the basal nuclei, including those in the central region of the epidermal proliferative units. One month later, the labeling index was reduced to 2%; 90% of the label-retaining cells were within a nuclear diameter of the central suprabasal column of the proliferative units. When mice were treated with 2 μg of TPA 1 month after labeling, mitotic label-retaining cells were found within 22 h after treatment. Seventy-five percent of the label-retaining cells remained on the basal layer through the 28-h experimental period. In contrast, the basal labeling index following a 1-h pulse of [3H]thymidine was 5%. Eighty-five percent of the labeled cells were found in the periphery of the proliferative units. By 4 days after pulse labeling, most of the originally labeled cells had divided, although vertical cross sections indicated that 92% remained on the basal layer. When mice were treated with TPA on day 4, labeled cells were rarely found in mitosis. Instead, about 60% of the labeled cells were displaced to the suprabasal layers. These observations suggest that 2 classes of epidermal basal cells have different early responses to TPA treatment: the label-retaining cells proliferate, and most of the 'maturing' cells continue to differentiate.
Bibliographical noteFunding Information:
Treatments such as 12-0-tetradecanoylphorbol-13-acetate (TPA) that effectively promote skin tumors in mice have in common the capacity to provoke an epidermal hyperplasia [1,5-7]. Coincident with the production of the hyperplasia is a transient increase in keratinization, soon followed by the induction in adult skin of a morphologically and biochemically immature epidermis . Recent evidence suggests that these changes might reflect alterations in the epidermal proliferative Manuscript received May 29, 1984; accepted for publication October 15, 1984. This work was supported by National Cancer Institute grants 20076, CA-34962, and CA-34890. Reprint requests to: Rebecca J. Morris, Ph.D., University of Texas System Cancer Center, Science Park-Research Division, P.O. Box 389, Smithville, Texas 78957. Abbreviations: TPA: 12-0-tetradecanoylphorbol-13-acetate