Production of urothelial tumors in the heterotopic bladder of rat by benzidine derivatives.
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.
Wang
C Y
CY
Department of Chemical Carcinogenesis, Michigan Cancer Foundation, Detroit 48201.
Zukowski
K
K
Yamada
H
H
Imaida
K
K
Lee
M S
MS
D000818:Animals; D001560:Benzidines / Q000633:toxicity*; D001711:Biotransformation; D002273:Carcinogens; D004260:DNA Repair; D004848:Epithelium / Q000473:pathology; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D001743:Urinary Bladder / Q000637:transplantation; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000473:pathology
D001560:Benzidines; D002273:Carcinogens; D011451:Prostaglandin-Endoperoxide Synthases