A qualitative ultrastructural study of the intercellular spaces between epithelial cells treated in vivo with DMBA

One of the features of epithelial dysplasia at the histological level is known as "loss of cellular adherence" in which adjacent epithelial cells appear more widely separated from each other than in normal tissues. In this study we examine the effects of the carcinogen DMBA on the epithelium of the hamster cheek-pouch with particular emphasis on the dimensions of the intercellular spaces. DMBA-induced lesions were processed for electron microscopy and assigned to hyperplasia, dysplasia and carcinoma groups, using defined criteria on toluidine blue-stained 1 micron Araldite sections. Untreated pouches were used as a control. At the light-microscopical level, intercellular spaces in hyperplastic epithelium appeared similar to those present in untreated tissue but increased progressively in dysplastic and carcinomatous lesions. Spaces were generally wider between basal and spinous cells than between granular cells, although wide variations were observed between tissue blocks demonstrating similar histological features and also within adjacent areas of the same block. At the ultrastructural level, untreated and hyperplastic tissue showed only occasional focal separations of adjacent plasma membranes; these spaces were more frequent between cells of lower strata. In sections from dysplasias and carcinomas, spaces were always extensive and were occupied by numerous villous or foliate membrane-bound cytoplasmic extensions. These were often attached to each other by desmosomes of apparently normal morphology but of a lower frequency than in untreated epithelium. The increased epithelial separation as indicated by the increased intercellular spaces during chemical carcinogenesis may be a result of any or all of the following factors: desmosomal disruption or their failure to develop; the production of cell-surface molecules which are less adhesive; inflammatory oedema and direct alterations on intercellular junctions and cell-surface components by infiltrating inflammatory cells.