Benzidine N-Glucuronidation by Human, Rat, and Dog Liver

Terry V. Zenser, Vijaya M. Lakshmi, Satram R. Babu, F. F. Hsu, Robert E. Kane, Bernard B. Davis

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Abstract

Hepatic N-glucuronidation is proposed to be an important pathway for metabolism of aromatic amine carcinogens and was assessed in human, rat, and dog. Benzidine and its monoacetylated product N-acetylbenzidine were glucuronidated. The latter was identified as an N’-glucuronide. Both glucuronides were acid labile with t1/2s of approximately 5 min at pH 5.3 and 37 °C. In plasma, the stability of both glucuronides increased. Irrespective of the detergent used to increase microsomal activity, the relative amount of glucuronidation was human > dog > rat N-Glucuronidation of N-diacetylbenzidine was not detected. Following incubation with 3H-benzidine, liver slices from all three species produced N-glucuronides. However, only human and rat slices produced N-acetylbenzidine N’-glucuronide. The stability of these N-glucuronides in plasma and their lability in acidic urine provides a mechanism by which these detoxified products are transported to the bladder and then recycled to the arylamine. A model is presented illustrating the effect of N-glucuronidation and the influence of N-acetylation on arylmono- and aryldi- amine-induced bladder carcinogenesis.

Original languageEnglish
Pages (from-to)145-152
Number of pages8
JournalPolycyclic Aromatic Compounds
Volume7
Issue number1-3
DOIs
StatePublished - Aug 1 1994

Keywords

  • aromatic amines
  • benzidine
  • bladder cancer
  • glucuronidation

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    Zenser, T. V., Lakshmi, V. M., Babu, S. R., Hsu, F. F., Kane, R. E., & Davis, B. B. (1994). Benzidine N-Glucuronidation by Human, Rat, and Dog Liver. Polycyclic Aromatic Compounds, 7(1-3), 145-152. https://doi.org/10.1080/10406639408014724