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.
Lakshmi
V M
VM
Geriatric Research, Education and Clinical Center (GRECC), Veterans Administration Medical Center, St Louis, MO 63125.
Mattammal
M B
MB
Spry
L A
LA
Kadlubar
F F
FF
Zenser
T V
TV
Davis
B B
BB
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