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Production of Urothelial Tumors in the Heterotopic Bladder of Rats by Instillation of N-Glucuronosyl or N-Acetyl Derivatives of N-Hydroxy-2-aminofluorene¹

Department of Chemical Carcinogenesis, Michigan Cancer Foundation, Detroit, Michigan 48201

Male F344 rats which had been implanted with a heterotopic bladder were randomly divided into four groups and their heterotopic bladders were instilled once a week for 30 weeks with 0.5 ml phosphate-buffered saline-dimethyl sulfoxide solution (4:1), or this solution containing 2 µmol N-methyl-N-nitrosourea, 1 µmol N-hydroxy-2-acetylaminofluorene (N-OH-AAF), or 1 µmol N-hydroxy-N-glucuronosyl-2-aminofluorene (N-OH-N-Gl-AF). These bladders were then instilled once a week for an additional 23 weeks with phosphate buffered saline solution without the addition of dimethyl sulfoxide. The animals were killed at the end of 53 weeks. Transitional cell carcinomas were observed in five of 37, 36 of 37, 15 of 35, and 36 of 38 rats of the control, N-methyl-N-nitrosourea, N-OH-AAF, and N-OH-N-Gl-AF groups, respectively. No histological alteration was observed in their natural bladders and no tumor was observed in the liver. As judged by kinetic measurements of the radioactive compounds, N-OH-AAF was removed much faster than N-OH-N-Gl-AF from the fluid of heterotopic bladder. The pH of the fluid in the bladder was between 7.1 and 7.4. The present study demonstrates the carcinogenicity of N-OH-N-Gl-AF and N-OH-AAF for rat bladder.

¹ This report from the Alfred Taubman Facility is supported by USPHS Grant CA 23800 and an institutional grant from the United Foundation of Detroit.

² To whom requests for reprints should be addressed, at Michigan Cancer Foundation, Meyer L. Prentis Cancer Center, Department of Chemical Carcinogenesis, 110 East Warren Avenue, Detroit, MI 48201-1379.

³ Present address: First Department of Pathology, Nagoya City University Medical School, Mizuho-cho, Mizuho-ku, Nagoya, Japan.

Received 1/15/87. Revised 3/25/87. Accepted 3/31/87.