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.
D015073:2-Acetylaminofluorene / Q000378:metabolism; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D001711:Biotransformation; D002849:Chromatography, Gas; D004790:Enzyme Induction / Q000187:drug effects; D005449:Fluorenes / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D010130:p-Aminohippuric Acid / Q000494:pharmacology
D005449:Fluorenes; D015073:2-Acetylaminofluorene; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; D010130:p-Aminohippuric Acid; D010634:Phenobarbital