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Luminal plasma membrane organization in rat urinary bladder urothelium after direct exposure in vivo to N-methyl-N-nitrosourea.

Adult female rat urinary bladders were exposed to N-methyl-N-nitrosourea in vivo. After 12 weeks, urothelial hyperplasia was established. Ultrastructural changes of the luminal plasma membrane were studied with thin sectioning and freeze-fracturing techniques. The mosaic pattern which is a characteristic specialization of the normal luminal plasma membrane and of cytoplasmic vesicles disappeared. The plasma membrane of the transformed urothelium was indistinguishable from an undifferentiated membrane in the following respects: thickness; apparent symmetry in cross-section; and distribution of intramembranous particles. Zonulae occludentes became permeable to colloidal lanthanum and appeared disassembled, while desmosomes developed concomitantly. These membrane changes implicate increased permeability and less adaptability of urothelial function to mechanical stress caused by bladder volume changes. The increased desmosome formation may indicate that squamous metaplasia is a feature of early malignant urothelium transformation. It is proposed that N-methyl-N-nitrosourea treatment induces a change in the plasma membrane assembly and specialization.