Changes in proliferating cell subpopulations and mitotic activity in human epidermal cultures treated with epithelial growth inhibitors.

Labeling of cultured human epidermal cells with [3H]thymidine has revealed a dramatic heterogeneity among sorted S-phase cells. Cell kinetic studies have shown that these differences in labeling intensity most probably reflect differences in the rate of DNA synthesis, and cycling basal cells may be divided into subpopulations on this basis. Studies with growth stimulators have suggested that these subpopulations are involved in cell renewal or population expansion during early differentiation of the keratinocyte. In the present study the effects of an epidermal growth inhibitor purified from an epidermis extract and a kidney epithelial growth inhibitor obtained from conditioned medium of BSC-1 cell cultures were investigated. Both agents were shown to cause a dramatic decrease in mitotic activity in the epidermal cultures and also to diminish the proportion of S-phase cells with a strong thymidine incorporation (high rate of DNA replication). The effect of the BSC-1 growth inhibitor was furthermore shown to be counteracted by epidermal growth factor and cholera toxin.