Pathogenesis, Histology, and Transplantability of Urinary Bladder Carcinomas Induced in Albino Rats by Oral Administration of N- [4-(5-Nitro-2-fury1)-2-thiazolyl] formamide

Thirty-five male Sprague-Dawley rats were fed 0.188% of N- [4-{5-nitro-2-furyl)-2-thiazolyl] formamide for 26 or 46 weeks. All of the rats survived 24 weeks or more and developed gross bladder carcinomas. Severe hyperplasia of the renal pelvis was observed in 19 rats, and carcinomas of the renal pelvis which invaded the kidney developed in 4 rats. The pathogenesis of these bladder carcinomas was studied in 70 female Sprague-Dawley rats fed 0.188% of N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide for 26 or 46 weeks. At frequent intervals, one rat from each group was sacrificed, and histologic comparisons of the bladder mucosa were made with bladders of rats fed the control diet. Hyperplasia of the transitional epithelium of the urinary bladder, developing in several areas of the mucosa, was observed 3 weeks after initiation of feeding the test compound. Squamous metaplasia and increased mucosal mitotic activity was seen after 8 weeks. Microscopic papillary or sessile transitional cell carcinomas were detected within 9 weeks, and small tumors localized all over the bladder mucosa were detectable grossly after 12 weeks. After 25 weeks the gross bladder tumors were 2 cm in diameter, and after 45 weeks they were 3—7 cm in diameter. One rat developed a metastatic pulmonary transitional cell carcinoma. Urinary bladder carcinomas which developed in male rats were transplanted s.c. into weanling female Sprague-Dawley rats. Grossly palpable tumors were present 3 weeks after transplantation, and the presence of squamous metaplasia increased the degree of transplantability. One recipient rat developed a metastatic pulmonary transitional cell carcinoma. N- [4-(5-Nitro-2-furyl)-2-thiazolyl] formamide appears to be one of the most effective urinary bladder carcinogens for both male and female Sprague-Dawley rats, providing carcinomas exhibiting all criteria of malignancy.