Contribution of theafulvins to the antimutagenicity of black tea: their mechanism of action.
Theafulvins were isolated from black tea aqueous infusions and their antimutagenic activity was evaluated against a number of food carcinogens. Theafulvins gave rise to a concentration-dependent inhibition of the mutagenicity of 2-amino-3-methylimidazo-[4,5-f]quinoline, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene, nitrosopyrrolidine and nitrosopiperidine, but, in contrast, the mutagenicity of aflatoxin B1 was enhanced. The mutagenicity exhibited by N'-methyl-N'-nitro-N-nitrosoguanidine and 9-aminoacridine was not influenced and weakly inhibited by theafulvins, respectively. The p-hydroxylation of aniline and the O-dealkylations of methoxy-, ethoxy- and, to a lesser extent, pentoxyresorufin were inhibited by theafulvins in a concentration-dependent manner. When microsomal metabolism was terminated after metabolic activation of the promutagens, incorporation of the theafulvins into the activation system did not modulate the mutagenic response. It is concluded that theafulvins play an important role in the antimutagenic activity of black tea by inhibiting cytochrome P450-dependent bioactivation of the carcinogens.
Catterall
F
F
School of Biological Sciences, University of Surrey, Guildford, UK.
Copeland
E
E
Clifford
M N
MN
Ioannides
C
C
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001564:Benzo(a)pyrene / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D020111:Chlorodiphenyl (54% Chlorine) / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000633:toxicity; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009242:N-Nitrosopyrrolidine / Q000633:toxicity; D009602:Nitrosamines / Q000633:toxicity; D010078:Oxazines / Q000378:metabolism; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D059808:Polyphenols; D011804:Quinolines / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013662:Tea / Q000737:chemistry*; D014812:Vitamin K / Q000494:pharmacology
D016587:Antimutagenic Agents; D002273:Carcinogens; D007093:Imidazoles; D009602:Nitrosamines; D010078:Oxazines; D010636:Phenols; D059808:Polyphenols; D011804:Quinolines; D013662:Tea; D020111:Chlorodiphenyl (54% Chlorine); D014812:Vitamin K; C086701:thearubigin; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D001564:Benzo(a)pyrene; D015127:9,10-Dimethyl-1,2-benzanthracene; C002743:N-nitrosopiperidine; C044943:pentoxyresorufin; D002392:Catechin; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D009242:N-Nitrosopyrrolidine