Ultrastructural Study on Changes of the Epithelial Cells of the Rat Bladder Induced by N-buty1-N-(4-hydroxybutyl) Nitrosamine Administration

Noh, Choong Hee; Kim, Young Kyoon

Abstract

Morphologic changes of the urinary bladder epithelium of the Wistar rats induced by oral administration of 0.05% solution of N-buty1-N-(4-hydroxybutyl) nitrosamine (BBN) were studied by means of light and electron microscopes. Hyperplasia was constantly obsessed in the animals administered with BBN for 4 weeks or more, and the hyperplastic area increased proportionally with the duration of BBN administration, but decreased in the 4-& 8-week groups after cessation of BBN administration. Papilloma and carcinoma developed in 87.5% and 37.5% after 12 weeks of BBN administration, respectively, and the figure increased continuously without further administration of BBN. Ultrastructurally, the superficial cells in the normal and hyperplastic epithelia were composed of both light and dark cells and the luminal surface was characterized by the presence of asymmetric unit membrane with knob like protrusions. In the hyperplastic epithelium there was increase in the number of surface dark cells with occasional vesicles in hinge regions. A transitional lesion between hyperplasia and papilloma was observed, being characterized by dark cells with numerous microvilli on surface and lateral cell membranes. The cytoplasm of the cells contained round or ovoid vesicular structures, and intercellular edema was also seen. The surface dark cells of papilloma were frequently exfoliated and the immature intermediate cells were exposed to the luminal surface, the cell membranes showing pleomorphic microvilli at surface and lateral walls. The proliferation of the intermediate cells was also pronounced. The papillary carcinoma showed stromal invasion with interruption of basal lamina, and nuclear and cytoplasmic pleomorphism. The above ultrastructural features support that the transitional cell carcinoma develops from the preceding hyperplasia-papilloma process and the alterations in the intracytoplasmic vesicles and asymmetric unit membrane provide the sequential changes on the cell permeability to result in an easy access to the subsequent exposure to the intravesical accumulation of carcinogen.