Absorption and protein binding of N-2-fluorenylacetamide and its metabolites in the bladder of rabbit.
To assess the reactivity of a bladder carcinogen, the absorption by the rabbit (male New Zealand White) bladder mucosa of N-2-acetylaminofluorene (AAF), N-hydroxy-2-acetyl-aminofluorene (N-OH-AAF), and the N-O-glucuronide of AAF (N-OGI-AAF), as well as binding to the protein and RNA of bladder mucosa, was measured in vivo and in vitro. Mucosal pieces incubated for 3 hours in medium containing a carcinogen demonstrated that the fluorene nucleus of both AAF and N-CH-AAF bound equally with cellular proteins, while N-OGI-AAF binding was lower. In the presence of an excess of beta-glucuronidase, however, N-OGI-AAF showed binding equivalent to its metabolic precursor. After a 3-hour instillation into the bladder lumen of radioactive carcinogens suspended in urine in vivo, transmural absorption of AAF and N-OH-AAF (90%) was substantial, while N-OGI-AAF was absorbed less (55%). The renal excretion during this period varied from 18 to 52% of the instilled radioactivity. There was little reactivity of these carcinogens with the mucosal RNA, both in vivo and in vitro. The metabolism of N-OH-AAF and N-OGI-AAF was such, both in vitro and in vivo, that the acetyl group was not included in the final protein-carcinogen complex in what appeared to be an enzyme reaction.
D015073:2-Acetylaminofluorene / Q000378:metabolism*; D000042:Absorption; D000107:Acetylation; D000818:Animals; D005449:Fluorenes / Q000031:analogs & derivatives* / Q000378:metabolism*; D005965:Glucuronates / Q000378:metabolism; D005966:Glucuronidase / Q000494:pharmacology; D006881:Hydroxyacetylaminofluorene / Q000031:analogs & derivatives* / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D011817:Rabbits; D001743:Urinary Bladder / Q000378:metabolism*
D005449:Fluorenes; D005965:Glucuronates; D006881:Hydroxyacetylaminofluorene; D012313:RNA; D015073:2-Acetylaminofluorene; D005966:Glucuronidase