Abstract
Theafulvins (TFu) isolated from black tea were antimutagenic in the Ames assay when tested against six indirect-acting food mutagens. The mechanism for the antimutagenic effects observed was by inhibition of the cytochrome P450 isoforms responsible for the bioactivation of the promutagens. TFu had no significant effect on the mutagenicity elicited by two direct-acting mutagens. Interestingly, TFu caused a synergistic increase in the mutagenic response elicited by the mycotoxin aflatoxin B1. A number of mechanisms appear responsible for this synergism which included a direct effect on the Salmonella typhimurium bacteria used in the assay and inhibition of the two principal detoxification pathways, namely epoxide hydrolase and glutathione S-transferase. A similar synergistic effect was apparent between the model mutagen N-nitrosopyrrolidine and polymeric, oligomeric, dimeric or monomeric procyanidins in the Ames assay. The mechanism for the synergistic effects appears to involve a direct interaction between the Salmonella typhimurium bacteria and the polyphenols. Polymeric and oligomeric procyanidins had no effect on the mutagenicity of the direct-acting mutagen MNNG but inhibited the mutagenic response elicited by two indirect-acting mutagens, namely IQ and benzo[a]pyrene. These antimutagenic effects were only apparent at the highest concentrations of the polyphenols tested (200 μg/plate), levels unlikely to be achieved in human tissues after dietary consumption. In contrast, dimeric and monomeric polyphenols had no significant effect on the same direct- or indirect-acting mutagens in the Ames test. The addition of milk to either black, decaffeinated black or green tea had no significant effect on the antimutagenic activity of the tea brews against a number of indirect- or direct-acting mutagens in the Ames test Finally, the pharmacokinetic evaluation of 3H-(+)-catechin and 3H-(-)-epicatechin following oral intake of dietary doses showed that the bioavailability of both compounds was less than 5%. After iv administration, the flavonoids were removed from the blood very rapidly and predominantly eliminated via the faeces.