Effects of black tea theafulvins on aflatoxin B(1) mutagenesis in the Ames test.
Black tea theafulvins, a fraction of thearubigins isolated from black tea aqueous infusions, potentiated the mutagenic activity of the mycotoxin aflatoxin B(1) in the Ames test, in the presence of a hepatic S9 activation system derived from Aroclor 1254-treated rats. In contrast, when the S9 activation system was replaced with isolated microsomes, theafulvins suppressed the mutagenicity of the mycotoxin. When microsomal metabolism was terminated after metabolic activation of the mycotoxin, incorporation of the theafulvins into the activation system reduced the mutagenic activity, whereas if it was added before termination of microsomal activity a potentiation of mutagenic response was observed. In in vitro studies, theafulvins inhibited epoxide hydrolase and glutathione S-transferase activities in a concentration-dependent manner. Finally, the mutagenicity of aflatoxin B(1) was much more pronounced in bacteria that were pre-exposed to theafulvins but from which they were subsequently washed off. It may be inferred from the above studies that the genotoxic synergy between aflatoxin B(1) and black tea theafulvins does not occur during the bioactivation of the carcinogen, but may partly be due to decreased deactivation of the reactive intermediate, aflatoxin B(1) 8,9-oxide, by conjugation with glutathione.
Catterall
Fenton
F
School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK.
Copeland
Emma
E
Clifford
Michael N
MN
Ioannides
Costas
C
D016604:Aflatoxin B1; D000818:Animals; D002273:Carcinogens; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004851:Epoxide Hydrolases / Q000737:chemistry; D005978:Glutathione / Q000737:chemistry; D005982:Glutathione Transferase / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000378:metabolism; D016296:Mutagenesis; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens; D010636:Phenols / Q000737:chemistry* / Q000494:pharmacology*; D059808:Polyphenols; D051381:Rats; D017208:Rats, Wistar; D012486:Salmonella typhimurium; D013662:Tea
D002273:Carcinogens; D009153:Mutagens; D010636:Phenols; D059808:Polyphenols; D013662:Tea; C086701:thearubigin; D002392:Catechin; D016604:Aflatoxin B1; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases; D005978:Glutathione