Effects of tumor promoters on the rate and commitment to terminal differentiation of subpopulations of murine keratinocytes.
The effects of skin-tumor-promoting and -nonpromoting agents on the kinetics of terminal differentiation of subpopulations of keratinocytes differing in buoyant density isolated from mice (SENCAR) that are very sensitive to 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion were investigated. Topical pretreatment of dorsal skin with complete (TPA), first-stage (calcium ionophore A23187) and second-stage (mezerein) tumor promoters, but not the hyperplastic agent ethylphenylpropiolate, accelerated the rate of terminal differentiation of keratinocytes with densities less than 1.074 g/cm3, but had little effect on cells with a greater density. Within 8.5 hr of TPA treatment, a period preceding mitosis, a large percentage of the most dense basal-cell keratinocytes (greater than or equal to 1.074 g/cm3) were converted to cells with a lower density, with a reduced plating efficiency and with an increased rate of differentiation, suggesting that TPA induces a subpopulation of basal cells to commit to terminal differentiation, and accelerates the rate of differentiation of committed cells.
D000001:Calcimycin / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient; D004224:Diterpenes; D007633:Keratins / Q000378:metabolism; D007700:Kinetics; D010703:Phorbol Esters / Q000494:pharmacology; D012867:Skin / Q000166:cytology* / Q000187:drug effects; D013729:Terpenes; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002273:Carcinogens; D004224:Diterpenes; D010703:Phorbol Esters; D013729:Terpenes; C011309:mezerein; D000001:Calcimycin; D007633:Keratins; D013755:Tetradecanoylphorbol Acetate