MARKED ANTIMUTAGENIC POTENTIAL OF AQUEOUS GREEN TEA EXTRACTS - MECHANISM OF ACTION

In the present study aqueous extracts of green tea, at the concentrati ons customarily consumed by humans, were evaluated for their antimutag enic activity against major classes of dietary and occupational carcin ogens. Green tea extracts caused a very marked and concentration-depen dent inhibition of the Aroclor 1254-hepatic S9-mediated mutagenicity o f heterocyclic amines (IQ and Glu-P-1) and polycyclic aromatic hydroca rbons (benzo[a]pyrene and 7,12- dimethylbenz[a]anthracene) and of the isoniazid-induced S9-mediated mutagenicity of nitrosamines (nitrosopip eridine and nitrosopyrrolidine). Similar inhibition was seen in the mu tagenicity of the two aromatic amines, namely 2-amino-fluorene and 2-a minoanthracene, whether Aroclor 1254-S9, isolated microsomes or cytoso l served as the activation system. Finally, the mutagenicity of the di rect-acting mutagens 9-aminoacridine and MNNG was also suppressed by g reen tea extracts, but the effect was less pronounced when compared wi th the indirect-acting mutagens. Green tea extracts caused a marked an d concentration-dependent decrease in the O-dealkylation of methoxyres orufin, ethoxyresorufin and pentoxyresorufin. A similar inhibition of the NADPH-dependent reduction of cytochrome c was also observed. Follo wing the termination of the microsomal metabolism of the various promu tagens, incorporation of green tea extracts into the activation system resulted in a comparatively modest inhibition of their mutagenic resp onse. It is concluded that aqueous extracts of green tea possess marke d antimutagenic potential against a variety of important dietary and e nvironmental mutagens. Two mechanisms appear to be responsible. The fi rst involves a direct interaction between the reactive genotoxic speci es of the various promutagens and nucleophilic tea component(s) presen t in the aqueous extracts. The second, and apparently more important m echanism, involves inhibition of the cytochrome P450-dependent bioacti vation of the promutagens. The inhibition of cytochrome P450 activity may be, at least partly, due to impairment of the electron flow from N ADPH to the cytochrome.