Marked antimutagenic potential of aqueous green tea extracts: mechanism of action.
In the present study aqueous extracts of green tea, at the concentrations customarily consumed by humans, were evaluated for their antimutagenic activity against major classes of dietary and occupational carcinogens. Green tea extracts caused a very marked and concentration-dependent inhibition of the Aroclor 1254-hepatic S9-mediated mutagenicity of heterocyclic amines (IQ and Glu-P-1) and polycyclic aromatic hydrocarbons (benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene) and of the isoniazid-induced S9-mediated mutagenicity of nitrosamines (nitrosopiperidine and nitrosopyrrolidine). Similar inhibition was seen in the mutagenicity of the two aromatic amines, namely 2-amino-fluorene and 2-aminoanthracene, whether Aroclor 1254-S9, isolated microsomes or cytosol served as the activation system. Finally, the mutagenicity of the direct-acting mutagens 9-aminoacridine and MNNG was also suppressed by green tea extracts, but the effect was less pronounced when compared with the indirect-acting mutagens. Green tea extracts caused a marked and concentration-dependent decrease in the O-dealkylation of methoxyresorufin, ethoxyresorufin and pentoxyresorufin. A similar inhibition of the NADPH-dependent reduction of cytochrome c was also observed. Following the termination of the microsomal metabolism of the various promutagens, incorporation of green tea extracts into the activation system resulted in a comparatively modest inhibition of their mutagenic response. It is concluded that aqueous extracts of green tea possess marked antimutagenic potential against a variety of important dietary and environmental mutagens. Two mechanisms appear to be responsible. The first involves a direct interaction between the reactive genotoxic species of the various promutagens and nucleophilic tea component(s) present in the aqueous extracts.(ABSTRACT TRUNCATED AT 250 WORDS)
Division of Toxicology, School of Biological Sciences, University of Surrey, Guildford, UK.
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Bu-Abbas
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Clifford
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Walker
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Ioannides
D000818:Animals; D016588:Anticarcinogenic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D016587:Antimutagenic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001711:Biotransformation / Q000187:drug effects*; D002273:Carcinogens / Q000493:pharmacokinetics / Q000633:toxicity; D065607:Cytochrome P-450 Enzyme Inhibitors; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000493:pharmacokinetics / Q000633:toxicity; D010078:Oxazines / Q000378:metabolism; D010936:Plant Extracts; D051381:Rats; D017208:Rats, Wistar; D012486:Salmonella typhimurium / Q000187:drug effects; D013662:Tea / Q000737:chemistry*; D014867:Water
D016588:Anticarcinogenic Agents; D016587:Antimutagenic Agents; D002273:Carcinogens; D065607:Cytochrome P-450 Enzyme Inhibitors; D009153:Mutagens; D010078:Oxazines; D010936:Plant Extracts; D013662:Tea; D014867:Water; C014180:resorufin