Inhibition of the mutagenicity of aromatic amines by the plant flavonoid (+)-catechin.
Addition of the plant phenolic flavonoid (+)-catechin to rat liver microsomes inhibited the mutagenicity of the aromatic amines 2-aminofluorene and 4-aminobiphenyl in the Ames test. Similarly, (+)-catechin decreased the mutagenicity of N-hydroxy-4-amino-biphenyl, the proximate carcinogen, but, in contrast, had no effect on the mutagenicity of other direct-acting carcinogens such as N-methyl-N'-nitro-N-nitrosoguanidine and 9-aminoacridine. In vitro addition of (+)-catechin gave rise to a dose-dependent inhibition of the cytochrome P-450-dependent benzphetamine N-demethylase and ethoxyresorufin O-deethylase activities. This was achieved by impairment of the electron flow from the reduced pyridine nucleotide to the cytochrome. However, administration of (+)-catechin to rats had no effect on the in vitro mixed-function oxidase activities. It is concluded that the (+)-catechin inhibits the mutagenicity of aromatic amines in the Ames test by interfering with their cytochrome P-450-dependent bioactivation and by direct interaction with the proximate carcinogen, but the former mechanism is unlikely to occur in vivo because the high doses of the flavonoid required are not achieved.
D000588:Amines / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000611:Aminobiphenyl Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002392:Catechin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005449:Fluorenes / Q000037:antagonists & inhibitors / Q000633:toxicity; D008297:Male; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D009153:Mutagens / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000588:Amines; D000611:Aminobiphenyl Compounds; D001578:Benzopyrans; D005449:Fluorenes; D009153:Mutagens; C006757:4-biphenylamine; C012177:2-aminofluorene; D002392:Catechin; D006899:Mixed Function Oxygenases