The effect of quercetin, a mutagenicity-enhancing agent, on the metabolism of 2-acetylaminofluorene with mammalian metabolic activation systems.
The effect of quercetin as the comutagen on 2-acetylaminofluorene (AAF) was investigated. AAF was metabolized with mammalian metabolic systems (S9 mix) in the presence or absence of quercetin in vitro, and its metabolites were determined by high-performance liquid chromatography. In the presence of quercetin, the total metabolic rate of AAF decreased compared with that in the absence of quercetin, whereas the formation of N-hydroxy-AAF (N-OH-AAF) and 2-aminofluorene (AF) increased. Since the main metabolic pathway of AAF is aryl-hydroxylation, it is suggested that the decrease of total metabolic rate of AAF is due to the inhibition of aryl-hydroxylation by quercetin. From these results, it seems probable that the comutagenic effect of quercetin on AAF is due to the inhibition of aryl-hydroxylation (the detoxifying pathway) and the promotion of N-hydroxylation and deacetylation (the activating pathway) in the AAF metabolism with S9 mix.
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D004357:Drug Synergism; D005419:Flavonoids / Q000494:pharmacology*; D005449:Fluorenes / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009154:Mutation / Q000187:drug effects*; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects
D005419:Flavonoids; D005449:Fluorenes; C012177:2-aminofluorene; D011794:Quercetin; D015073:2-Acetylaminofluorene