Transmission electron microscopic studies of events in a model of experimental bladder carcinoma in the rat were reported and compared with normal bladder structure. Epithelial events during carcinogenesis were briefly discussed in terms of sequential changes in cell-to-cell relationships, asymmetric unit membrane, the Golgi apparatus, and keratinization. Nonepithelial but related events pertaining to the lamina densa of the basement membrane and the subepithelial capillary vessels were also described and illustrated.
It is suggested that many of the changes recorded may reflect rapid epithelial growth and turnover rather than specific morphological expressions of carcinogenesis. On the other hand, some of the recorded events such as the very early injury to the Golgi apparatus and the occurrence of microvilli on the surfaces of all epithelial cells cannot be so explained and may represent a more specific morphological response to the carcinogen. The significance of the nonepithelial events such as the multiplication and thickening of the lamina densa and the proliferation of abnormal capillaries surrounded by their own multilayered lamina densa was discussed. The significance of squamous metaplasia was considered as a possible factor in formation of invasive carcinoma. It was suggested that most papillary tumors and invasive cancer are perhaps not related except in time and space.
Ultrastructural changes observed in human hyperplastic urothelium and in papillary tumors were briefly summarized, and points of similarity with the experimental system were noted. The possible significance of these observations was discussed in the light of Cairns' theory of epithelial carcinogenesis. Full elucidation of the significance of many of the changes described as causing and effecting malignant transformation clearly requires additional work.
Presented at the National Bladder Cancer Conference, November 28 to December 1, 1976, Miami Beach, Fla.