Induction and modification of rat liver microsomal arylamide N-hydroxylase by various pretreatments.

Razzouk, C.;Batardy-Grégoire, M;Roberfroid, Marcel
(1982) Molecular Pharmacology — Vol. 21, n° 2, p. 449-457 (1982)

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  • Razzouk, C.
    Author
  • Batardy-Grégoire, M
    Author
  • Roberfroid, MarcelUCLouvain
    Author
Abstract
3-Methycholantrene, benzoanthracene, benzo[e]pyrene, and pyrene induce N-hydroxylase activity and modify the enzyme by increasing its apparent Km. As exemplified by the effect of 3-methylcholanthrene, the polycyclic aromatic hydrocarbons also induce other mixed-function oxidases such as aryl hydrocarbon hydroxylase and the various arylamide C-hydroxylases. Acute or chronic pretreatment of rats with acetylaminofluorenes induces N-hydroxylase and modifies the enzyme affinity by decreasing its apparent Km. Among the various-position isomers, 4-acetylaminofluorene is completely inactive and 2-acetylaminofluorene is the most potent. Its effect is both dose- and time dependent, and it seems to be specific for N-hydroxylase, the same pretreatment having no effect on arylhydrocarbon hydroxylase or arylamide C-hydroxylases. After simultaneous treatment of rats with 3-methylcholanthrene and 2-acetylaminofluorene, even though N-hydroxylase activity as measured on hepatic microsomes in vitro is significantly induced, the urinary excretion of N-hydroxy-2-acetylaminofluorene is significantly reduced over a 24-hr period. This observation is discussed in relationship to the well-known inhibitory effect of 3-methylcholanthrene on the hepatocarcinogenicity of 2-acetylaminofluorene.
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Razzouk, C., Batardy-Grégoire, M., & Roberfroid, M. (1982). Induction and modification of rat liver microsomal arylamide N-hydroxylase by various pretreatments. Molecular Pharmacology, 21(2), 449-457. https://hdl.handle.net/2078.5/52884 (Original work published 1982)