INDUCTION, ACTIVATION, AND INHIBITION OF HAMSTER AND RAT-LIVER MICROSOMAL ARYLAMIDE AND ARYLAMINE N-HYDROXYLASE

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (10) , 3540-3546
Abstract
By applying a new and highly sensitive assay for measuring N-hydroxy metabolites, the biochemical properties of the microsomal N-hydroxylase from control and 3-methylcholanthrene-treated rat and hamster liver were analyzed. Due to a difference in enzyme affinity, the metabolic activation of acetylaminofluorene is more pronounced than that of aminofluorene, a fact which correlates with the difference in the carcinogenic potency of the 2 compounds. Arylamine N-hydroxylase differs qualitatively and quantitatively from arylamide N-hydroxylase mainly in terms of sensitivity to various in vitro inhibitors. 7,8-Benzoflavone and 3-methylcholanthrene are strong inhibitors of liver microsomal N-hydroxylases. This effect could partly explain the inhibition of the hepatic tumorigenicity of acetylaminofluorene in animals simultaneously fed 3-methylcholanthrene. The metabolism of acetylaminofluorene proceeds via both ring- (C-1, C-3, C-5, or C-7) and N-hydroxylation. There is clear reciprocal interaction between these various microsomal pathways. The apparent increase in Km following pretreatment of the rat with 3-methylcholanthrene is due to competitive inhibition of the N-hydroxylase by some of the C-hydroxy metabolites. This effect is not seen in hamster liver.