Production of urothelial tumors in the heterotopic bladder of rat by benzidine derivatives.

Abstract

Male Fischer rats which had been implanted with a heterotopic bladder were randomly divided into five groups and their heterotopic bladders were instilled once a week for 20 weeks with 0.5 ml phosphate-buffered saline:dimethyl sulfoxide solution (4:1) or this solution containing 1 mumol benzidine (BZ), N'-hydroxy-N-acetylbenzidine, the N'-glucuronide of N'-hydroxy-N-acetylbenzidine, or the N-glucuronide of N-hydroxy-2-aminofluorene. These bladders were then instilled once a week for an additional 30 weeks with the phosphate-buffered saline without dimethyl sulfoxide. The experiment was terminated at the end of 50 weeks. Transitional cell carcinomas were observed in 1 of 39 (control), 1 of 29 (BZ), 18 of 30 (N'-hydroxy-N-acetylbenzidine), 28 of 28 (N'-hydroxy-N-acetylbenzidine N'-glucuronide), and 24 of 29 (N-hydroxy-2-aminofluorene N-glucuronide) rats. No histological alterations were observed in their natural bladders. These results demonstrate the urothelial carcinogenicity of the N-hydroxy metabolites of BZ and suggest that N'-hydroxy-N-acetylbenzidine N'-glucuronide may play a major role in the initiation of urothelial carcinogenesis by BZ in humans.

• Authors: C Y Wang, K Zukowski, H Yamada, K Imaida, M S Lee
• Journal: Cancer research (Cancer Res) Vol. 50 Issue 10 Pg. 2868-71 (May 15 1990) ISSN: 0008-5472 [Print] United States
• PMID: 2110501 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Benzidines
• Carcinogens
• Prostaglandin-Endoperoxide Synthases

Topics

• Animals
• Benzidines (toxicity)
• Biotransformation
• Carcinogens
• DNA Repair
• Epithelium (pathology)
• Male
• Prostaglandin-Endoperoxide Synthases (metabolism)
• Rats
• Rats, Inbred Strains
• Structure-Activity Relationship
• Urinary Bladder (transplantation)
• Urinary Bladder Neoplasms (chemically induced, pathology)