Ultrastructural analysis of epidermal hyperplasia induced by multiple 12-0-tetradecanoyl-phorbol-13-acetate (TPA) treatment of mouse skin

Stationary epidermal hyperplasia induced by exposure of mouse skin to 1-6 TPA applications was analyzed by electron microscopy and found to be of two types. Intermingled orderly and irregularly stratified hyperplastic regions observed prominently after a single TPA application gave way, on multiple treatment, to epidermal hyperplasia populated by either cuboidal cells with expanded cytoplasm or by highly polar, narrow, tall and pleomorphic cells. Both cell types were poorly differentiated and displayed a paucity of intact desmosomal junctions, resulting in an incohesive tissue structure in which a number of phenotypic variants were expressed. The variants were markedly less mature than the adjacent cells and showed basal cell phenotype, acquisition of secretory activity or a disturbed mitotic process, resulting in the formation of binucleated cells. The observations suggest that the disturbed mitotic process, poor cellular differentiation and induction of metaplasia could be the mode by which an initiated cell may express its tumor phenotype and escape differentiation during the early stage of TPA promotion