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

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.