The N-hydroxylation and ring-hydroxylation of 4-aminobiphenyl in vitro by hepatic mono-oxygenases from rat, mouse, hamster, rabbit and guinea-pig

Xenobiotica. Jul-Aug 1980;10(7-8):469-81. doi: 10.3109/00498258009033782.

Abstract

1. An analytical h.p.l.c. method has been developed which permits the separation and quantification of the in vitro metabolites of 4-aminobiphenyl (4-ABP). The method employs gradient elution from a reverse phase column. 2. The major metabolite in vitro of 4-ABP in liver fractions from rat, mouse, guinea-pig, rabbit and hamster was N-hydroxy-4-aminobiphenyl. 3. The observation that liver fractions from the guinea-pig are very effective in the n-hydroxylation of 4-ABP is in excellent agreement with the 1966 report from Kiese's laboratory, showing that the N-hydroxylation of 4-ABP is an important metabolic pathway in vivo in this species. 4. The ortho-phenol, 3-hydroxy-4-aminobiphenyl was also an important metabolite in each species except guinea-pig and rabbit. 5. Hydroxylation at the 4' and 2' positions was a minor pathway in all species studied. 6. Aroclor 1254 was a potent inducer of N-hydroxylation in rat, mouse and guinea-pig but not hamster and rabbit. Phenobarbital induced N-hydroxylation in rabbit and guinea-pig but not rat, while methylcholanthrene induced in rat and guinea-pig but not rabbit.

MeSH terms

  • Aminobiphenyl Compounds / metabolism*
  • Aminobiphenyl Compounds / pharmacology
  • Animals
  • Aroclors / pharmacology
  • Chlorodiphenyl (54% Chlorine)
  • Chromatography, High Pressure Liquid / methods
  • Cricetinae
  • Enzyme Induction
  • Guinea Pigs
  • Hydroxylation
  • Male
  • Methylcholanthrene / pharmacology
  • Mice
  • Microsomes, Liver / enzymology*
  • Mixed Function Oxygenases / antagonists & inhibitors
  • Mixed Function Oxygenases / biosynthesis
  • Mixed Function Oxygenases / metabolism*
  • Rabbits
  • Rats

Substances

  • Aminobiphenyl Compounds
  • Aroclors
  • Chlorodiphenyl (54% Chlorine)
  • 4-biphenylamine
  • 3-hydroxy-4-aminobiphenyl
  • Methylcholanthrene
  • N-hydroxy-4-aminobiphenyl
  • Mixed Function Oxygenases
  • 4-aminobiphenyl N-hydroxylase