Induction of urinary bladder urothelial cancers in the rabbit by dibutylnitrosamine with an artificial bladder calculus as cocarcinogen

Thirteen rabbits received liquid dibutylnitrosamine (DBN) s.c. at a dosage of 400 mg/kg body weight once a week for a maximum of 16 months to induce transitional cell carcinomas (TCC) of the bladder. In five of these rabbits, 4 months after starting the injection of DBN an artificial stone prepared from a methylmethacrylate 2-component plastic material was implanted into the bladder. Four rabbits developed TCC of the bladder, with latency periods of 15-18 months. These tumors were found in two of the five (40%) rabbits with stones and in two of the eight (25%) rabbits without stones. The stone-bearing animals had more deeply infiltrating tumors, although the tumor induction times were comparable. Within a maximum observation period of 28 months there were no lymphogenous or hematogenous metastases. Another two rabbits showed benign urothelial changes presenting as simple hyperplasia and von Brunn's nests after 4 and 4.5 months, respectively. In two rabbits we found malignant tumors located extravesically, in the lungs and the kidney. The results of our study confirm the feasibility of TCC induction in rabbits by DBN administered s.c. Additional implantation of an artificial bladder stone acting as a co-carcinogen does not lead to a larger number of tumors, but does seem to enhance the degree of TCC induction in the bladder.