Enhancement of chemically induced bladder carcinoma by cyclosporin A.

Abstract

The effects of cyclosporin A (CsA) on the induction of bladder carcinoma were investigated in Wistar rats using N-butyl-N (4 hydroxybutyl) nitrosamine (BBN) as a known initiator of carcinogenesis. Rats treated with 0.05% BBN + 5 mg/kg per day CsA or 0.05% BBN + 12.5 mg/kg per day CsA developed a dose-dependent (two to fourfold) enhancement of bladder tumor expansion and infiltration as compared to those treated with 0.05% BBN alone. In control rats receiving CsA at doses of 5 mg/kg per day or 12.5 mg/kg per day, no bladder carcinoma occurred. All CsA-treated groups, with or without 0.05% BBN, displayed slight or moderate medullary atrophy of the thymus. The results indicate that immunosuppression with CsA enhances the induction of bladder tumors by BBN. Furthermore, the immunosurveillance theory that effective expression of the immune response may be important in the control of tumor development was confirmed in the carcinogenesis of epithelial cell tumors.