Lack of carcinogenicity of 2-aminofluorene, its glucuronide and the glucuronide of N-hydroxy-2-acetylaminofluorene in heterotopic bladder of the rat.
The role of 2-aminofluorene and its N-glucuronide and the O-glucuronide of N-hydroxy-2-acetylaminofluorene in the bladder carcinogenesis by 2-aminofluorene were investigated. These compounds were injected into heterotopically transplanted bladders of male rats at a weekly dose of 1 mumol for 20 weeks. The experiment was terminated at the end of 50 weeks. The results showed that none of these compounds were carcinogenic in the heterotopically transplanted bladder. The O-glucuronide was not carcinogenic even when it was administered in a phosphate saline (pH 8.0), that favors the activation of this compound. The N-glucuronide of N-hydroxy-2-aminofluorene, a positive control, produced urothelial tumors. These results are consistent with the hypothesis that the N-glucuronides of hydroxylamines, but not the O-glucuronides of hydroxamic acids, are responsible for bladder carcinogenesis by arylamines.
Wang
C Y
CY
Department of Chemical Carcinogenesis, Michigan Cancer Foundation, Detroit 48201.
Imaida
K
K
Zukowski
K
K
Lee
M S
MS
D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D005449:Fluorenes / Q000633:toxicity*; D006881:Hydroxyacetylaminofluorene / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D016042:Transplantation, Heterotopic; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology / Q000637:transplantation*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced*
D002273:Carcinogens; D005449:Fluorenes; C012177:2-aminofluorene; D006881:Hydroxyacetylaminofluorene; C067682:2-aminofluorene N-glucuronide