Metabolism of 2-acetylaminofluorene. I. Metabolism in vitro of 2-acetylaminofluorene and 2-acetylaminofluoren-9-one by hepatic enzymes.
1. 2-Acetylaminofluorene (AAF) was converted by rat liver microsomal and cytosolic enzymes to 2-aminofluorene (AF), 2-glycoloylaminofluorene (GAF), 2-acetylaminofluoren-3-, -7-, and -9-ol (3-, 7-, 9-hydroxy-AAF), and 2-acetylaminofluoren-9-one (AAF-9-one). In addition, a new metabolite MX1 was detected. 2. AAF was converted by rabbit liver microsomal and cytosolic enzymes to N-hydroxy-AAF, GAF, 5-, 7-, and 9-hydroxy-AAF, AAF-9-one, 5- and 7-hydroxy-AAF-9-one (new compounds), and AF, indicating species differences in the N- and ring-hydroxylation of AAF and secondary oxygenation of AAF. In addition, an unknown metabolite MX2 was detected. 3. AAF-9-one was converted by rat liver microsomal and cytosolic enzymes to optically active 9-hydroxy-AAF and 7-hydroxy-AAF-9-one; in addition MX1 was found. 4. Rabbit liver microsomal and cytosolic enzymes converted AAF-9-one to 2-aminofluoren-9-one (AF-9-one), 9-hydroxy-AAF, N-hydroxy-AAF-9-one, GAF-9-one, 7-hydroxy-AAF-9-one, and 7,9-dihydroxy-AAF. In addition, metabolite MX1 and its dihydro-dihydroxy derivative were found. 5. These results indicate that AAF and AAF-9-one have common metabolic pathways, as AAF after primary oxygenation to 9-hydroxy-AAF and partial dehydrogenation to AAF-9-one, undergoes secondary oxygenation to 7-hydroxy-AAF-one and MX1 as well as the corresponding dihydro-dihydroxy derivatives.
Lenk
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Walther Straub-Institut für Pharmakologie und Toxikologie, LM-Universität, München, Germany.
Rosenbauer-Thilmann
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D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives* / Q000378:metabolism*; D000818:Animals; D002273:Carcinogens / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D005260:Female; D006900:Hydroxylation; D008099:Liver / Q000201:enzymology*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010634:Phenobarbital / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical
D002273:Carcinogens; C081265:2-acetylaminofluoren-9-one; D009249:NADP; D008748:Methylcholanthrene; D015073:2-Acetylaminofluorene; D010634:Phenobarbital