Ultrastructure of cell junctions in FANFT-induced urothelial tumors in urinary bladder of Fischer rats

The ultrastructure of intercellular junctions in normal Fischer rat urothelium was compared with that in noninvasive (stage O) and invasive (stage A-B2) urinary bladder tumors induced with the carcinogen N-(4-(5-nitro-2-furyl)-2-thiazoly) formamide (FANFT). Zonulae occludentes of normal urothelium appeared as a continuous belt of three to five parallel strands interconnected by intramembranous fibrils as seen in freeze-fracture replicas. In noninvasive FANFT tumors, some zonulae occludentes were focally expanded in size whereas others were markedly attenuated. With the progression of these tumors into invasive tumors, zonulae occludentes were discontinuous, thus becoming fasciae or maculae occludentes. Gap junctions of both the PF-1 and PF-2 types were observed in normal Fischer rat bladder urothelium and occurred either separately or in close proximity. In freeze-fracture replicas, the intramembrane particles of PF-1 gap junctions were often in a hexagonal array with a center to center spacing of 9 to 10 nm., whereas those of PF-2 gap junctions were irregularly arranged with a center to center spacing of approximately 20 nm. FANFT tumors contained PF-1 gap junctions which appeared normal but they were devoid of PF-2 gap junctions. Desmosomes, the most frequently encountered type of intercellular junctions in normal and neoplastic urothelium, were morphologically similar to those described in other epithelia. In normal urothelium, the number of desmosomes increased with cell maturation from basal to superficial cells. In FANFT tumors, the average size and number of desmosomes increased with the degree of squamous differentiation. Regional loss of desmosomes was observed in invasive tumors. Similarly, there was a regional loss of hemidesmosomes. The ultrastructure of intercellular junctions is similar for both rat and human noninvasive transitional cell carcinomas and squamous cell carcinomas. Thus, the rat model provides an appropriate system for the study of relationships between junctional alterations and early stages of bladder carcinogenesis.