Mutagenicity modulating effect of quercetin on aromatic amines and acetamides.
The effect of quercetin on the mutagenicity of 32 kinds of aromatic amines and their acetamides were investigated using Salmonella typhimurium TA98 with a mammalian metabolic activation system (S9 mix). Quercetin enhanced the mutagenicity of the tricyclic aromatic amines (aminofluorene, aminoanthracene and aminophenanthrene) and their acetamides by 1.2-5.9-fold. Whereas, quercetin depressed the mutagenicity of aniline derivatives, biphenyl derivatives, and bi- and tetra-cyclic amino derivatives. The modulation of mutagenicity of Trp-P-1, Trp-P-2, Glu-P-1 and Glu-P-2 (heterocyclic amines) by quercetin were liable to be affected by the content of S9 in the S9 mix. It seems that quercetin does not have the same effect as norharman, because quercetin did not enhance the mutagenicity of aniline. It is suggested that the modulation of the mutagenicity of aromatic amines and acetamides is caused by the modulation of the balance between the mutagenic activation and inactivation in the metabolism of these amines and acetamides in the presence of quercetin. In this modulation, quercetin may participate through its effects on the promotion of N-hydroxylation and the inhibition of arylhydroxylation and transacylation. The presence of tricyclic aromatic rings of amines and acetamides is a structural requirement for the mutagenicity enhancement by quercetin.
Ogawa
S
S
Kyoto Pharmaceutical University, Japan.
Hirayama
T
T
Fujioka
Y
Y
Ozasa
S
S
Tokuda
M
M
Hirai
K
K
Fukui
S
S
D000577:Amides / Q000008:administration & dosage / Q000633:toxicity*; D000588:Amines / Q000008:administration & dosage / Q000633:toxicity*; D001711:Biotransformation; D004357:Drug Synergism; D005419:Flavonoids / Q000633:toxicity*; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009154:Mutation / Q000187:drug effects*; D011794:Quercetin / Q000008:administration & dosage / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
D000577:Amides; D000588:Amines; D005419:Flavonoids; D011794:Quercetin