In many tissues, programmed cell death plays an important role, under both physiological and pathological conditions, in embryogenesis, metamorphosis, normal tissue turnover, and carcinogenesis. Human oral epithelium renewal is a typical example of the active participation of a cell in its own death process. Cells arising from mitotic activity in the stratum germinativum of the oral epithelium continuously migrate upwards to the stratum corneum, where dead cells are eventually desquamated. Cell death by apoptosis, a mode of cell death with characteristic morphologic features, is considered a major mechanism of programmed cell death, which is thought to be involved in normal development. We investigated morphological changes of nuclei during cell death in human oral epithelium in vivo and in cultured cells from oral epithelium. During cellular progression in stratified squamous epithelium, morphologically altered nuclei, which were flat and had rough contents, were observed in the granular layer. Morphological changes in nuclei were incompatible with typical apoptosis characterized by condensation of chromatin nuclear fragmentation, or both. In contrast, some cultured keratinocytes died while showing a pattern of apoptosis after treatment with bleomycin, a anti-cancer drug effective against squamous cell carcinoma. In addition, several modes of cell death unable to be classified as apotosis or necrosis were observed both in cultured oral keratinocytes and in human oral epithelium
in vivo. The results suggest that the major mode of cell death during differentiation of oral epithelium may not be apoptosis, and that other types of cell death, which are not known yet, may be involved in the development of oral epithelium, oral epithelium-derived carcinomas and cell death induced by treatment with therapeutic agents effective against oral epithelium-derived carcinomas.
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