A nude rat model for in vivo studies of human transitional cell carcinogenesis

A xenograft system was developed for studying experimental carcinogenesis of human transitional cells in vivo. Segments of human ureters were tied to an injection port, ligated at the opposite end, implanted into gamma-irradiated nude rats and weekly irrigated through the injection port with fresh PBS solution. Such implants maintained the normal histologic appearance of human urothelium for at least 20 weeks in vivo in the nude rats. In situ hybridization with a human repetitive sequence DNA probe showed that the urothelium and the submucosal connective tissue and smooth muscle were of human origin. The urothelial lining was positive with an immunohistochemical reaction for acidic cytokeratins. This model allows for the long-term direct exposure of human urothelium to bladder carcinogens for the purpose of induction of human transitional cell tumors.