Metabolism and disposition of benzidine in the dog.
The dog is an animal model for assessing aromatic amine-induced bladder cancer. For this reason, metabolism and disposition of benzidine in dog was assessed. Dogs were administered a 1 mg/kg i.v. dose of [3H]benzidine (16.4 mCi/mmol). The plasma t1/2 of the radiolabeled material (benzidine plus metabolites) was significantly longer (approximately 3 h) than authentic benzidine (less than 30 min). During the 5 h experiment, the majority of radiolabel was associated with bile, urine and carcass. Bladder transitional epithelium exhibited a consistently higher concentration of bound radioactivity than bladder muscle. A significant amount of binding was observed in DNA from liver, kidney and bladder. DNA from bladder transitional epithelium exhibited the highest concentration of radioactivity. Approximately 30% of the radioactivity recovered following HPLC of urine or bile was identified as unmetabolized benzidine. 3-Hydroxybenzidine was a major metabolite identified in bile (8%) but not urine. Urine samples treated with acid, base or sulfatase yielded 3-hydroxybenzidine (6%) as a major hydrolysis product. Similar treatment of bile samples did not result in increased amounts of 3-hydroxybenzidine. Neither N-acetylated nor N-methylated metabolites of benzidine were observed in urine or bile. Thus, considerable metabolism of benzidine occurs in dogs by pathways that are yet to be determined.
Geriatric Research, Education and Clinical Center (GRECC), Veterans Administration Medical Center, St Louis, MO 63125.
V M
VM
Lakshmi
M B
MB
Mattammal
L A
LA
Spry
F F
FF
Kadlubar
T V
TV
Zenser
B B
BB
Davis
D000818:Animals; D001560:Benzidines / Q000378:metabolism / Q000493:pharmacokinetics*; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism; D004285:Dogs; D005260:Female; D006207:Half-Life; D011865:Radioisotope Dilution Technique; D014018:Tissue Distribution; D014316:Tritium
D001560:Benzidines; D014316:Tritium; C029876:benzidine; D004247:DNA