Metabolism and disposition of benzidine in the dog.
Metabolism and disposition of benzidine in the dog.
复制标题
联苯胺在狗体内的代谢和处置。
DOI:
10.1093/carcin/11.1.139
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发表时间:
1990
期刊:
影响因子:
4.7
通讯作者:
Davis,BB
中科院分区:
文献类型:
--
作者:
Lakshmi,VM;Mattammal,MB;Spry,LA;Kadlubar,FF;Zenser,TV;Davis,BB
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 t½ of the radiolabeled material (benzidine plus metabolites) was significantly longer (∼3 h) than authentic benzidine (<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 umnetabolized benzidine. 3-Hydroxy-benzidine 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. NeitherN-acetylated norN-methylated metabolites of benzidine were observed in urine or bile. Thus, considerable metabolism of benzidine occurs in dog by pathways that are yet to be determined.