Metabolism and disposition of benzindine in the dog
| Autor: | Terry V. Zenser, Leslie A. Spry, B B Davis, Vijaya M. Lakshmi, Michael B. Mattammal, Fred F. Kadlubar |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Radioisotope Dilution Technique
Cancer Research medicine.medical_specialty Metabolite Urine Tritium chemistry.chemical_compound Dogs Internal medicine medicine Animals Bile Toxicokinetics Tissue Distribution Biotransformation Chromatography High Pressure Liquid Carcinogen Kidney Bladder cancer Benzidines DNA General Medicine Metabolism medicine.disease Benzidine medicine.anatomical_structure Endocrinology chemistry Female Half-Life |
| Zdroj: | Carcinogenesis. 11:139-144 |
| ISSN: | 1460-2180 0143-3334 |
| DOI: | 10.1093/carcin/11.1.139 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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