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Effects of Urine and Continued Exposure to Carcinogen on Progression of Early Neoplastic Urinary Bladder Lesions¹

Department of Urology, Indiana University School of Medicine, Indianapolis, Indiana 46223 [R. G. R.], and Departments of Urology [M. O. H., J. T. G.] and Pathology [R. O.], Northwestern University Medical School, Chicago, Illinois 60611

Based on reports of regression of superficial bladder tumors after urinary diversion, a study was designed to measure the effects of urine and continued exposure to carcinogen on the incidence of progression of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide-induced early urinary bladder lesions to invasive tumor. After being fed 0.2% N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide diet for 14 weeks, one-half of the male Fischer rats had urinary diversion by ureterosigmoidostomy, and the remainder were sham operated. One-half of each of these two groups was continued on the N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide diet while the remaining animals were fed regular chow postoperatively. One-half of each of the four groups was sacrificed at 3 months, and the remainder were sacrificed at 6 months after ureterosigmoidostomy or shamoperation. The incidence and mean number of tumors as well as the incidence of invasive tumor were tabulated.

The combined 3- and 6-month data indicate that excreted carcinogen in the urine influences progression of the preinvasive lesions more than urine alone or systemic carcinogen alone. However, urine alone had a significant effect (p < 0.025) on tumor incidence (8 of 19 sham-operated animals with tumor versus 1 of 18 diverted animals with tumor). Urine acts as a promoter in this experimental system. These findings may have clinical applications in the treatment of early transitional cell carcinoma.

¹ This work was supported by USPHS Grant CA 14649 through the National Bladder Cancer Project and by Cancer Center Support Grant CA 15145 through the National Cancer Institute and the Northwestern University Cancer Center.

² To whom requests for reprints should be addressed, at Department of Urology, 1100 West Michigan, Indianapolis, Ind. 46223.

Received 1/ 4/80. Accepted 8/29/80.