Enhancement of the mutagenicity of 2-acetylaminofluorene by flavonoids and the structural requirements.
The enhancing effects of 12 kinds of flavonoids on the mutagenicity of 2-acetylaminofluorene (AAF) in Salmonella typhimurium TA98 were investigated. In the mixed applications of AAF (22.4 nmoles/plate) with flavonoids (31.4-45.0 nmoles/plate) in the presence of a mammalian metabolic activation system (S9 mix), morin, galangin, flavonol, kaempferol, quercetin and myricetin enhanced the mutagenicity of AAF by 3.3-10.2-fold. The potency of the mutagenicity enhancing effects increased in the described order. For the mutagenicity-enhancing effects of the flavonoids on AAF, the flavonol structure, including the free 3-hydroxyl group and the 2,3-double bond, were essential. In the quercetin analogues, the 5-hydroxyl group was also essential. Further, the numbers of the hydroxyl groups substituted at the 3', 4' and 5'-positions in the B-ring contributed to an increase of the enhancing effect, whereas the substitution of a hydroxyl group at the 2'-position depressed the potency of the effect.
D015073:2-Acetylaminofluorene / Q000494:pharmacology*; D000818:Animals; D001711:Biotransformation; D004357:Drug Synergism; D005419:Flavonoids / Q000378:metabolism / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects*; D013329:Structure-Activity Relationship
D005419:Flavonoids; D015073:2-Acetylaminofluorene