Marked antimutagenic potential of aqueous green tea extracts: mechanism of action

Abstract

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)

Heterocyclic Aromatic Amines Heterocomplexation with Biologically Active Aromatic Compounds and Its Possible Role in Chemoprevention

“…The latter should augment rather than diminish HCAs genotoxicity by increased HCAs bioactivation ratio to highly reactive arylnitrenium intermediates, suggesting that mechanisms other than the modulation of phase I enzymes can be involved in observed protective action. The inhibitory effects of tea extracts towards promutagens (IQ, Glu-P-1) as well as directacting mutagens (9-aminoacridine and N-methyl-N-nitro-N-nitrosoguanidine) further support the hypothesis that protective effects of CAF cannot be fully explained by its influence on xenobiotic activation system [80]. The presence of mechanisms additional to the inhibition of cytochrome P450 enzymatic activity was also suggested by Chen and Yen [73].…”

Fractionation of green tea extracts: correlation of antimutagenic effect with flavanol content

“…Overall, it may be concluded from these studies that components other than the Ña-vanols are the major antimutagenic components present in green tea. A combination of two mechanisms, namely inhibition of the cytochrome P450 isoforms involved in the bioactivation of carcinogens and trapping of genotoxic metabolites are responsible for the antimutagenic activity of green tea (Bu-Abbas et al 1994). It is possible that Ñavanols play a role in only one of these two mechanisms, thus explaining the lack of correlation between antimutagenic potential of the tea fractions and Ñavanol content.…”

“…Microsomal metabolism was terminated by the addition of 100 kl of menadione (900 kM) and a second 20 min preincubation was carried out. Menadione is a potent inhibitor of the NADPH-dependent bioactivation of chemical carcinogens (Bu-Abbas et al 1994). Top agar was added and the mixture was poured onto minimal agar plates which were incubated for 48 h at 37¡C to allow revertants to develop into colonies.…”

“…mutagens including nitroso compounds, aromatic and heterocyclic amines, mycotoxins and polycyclic aromatic hydrocarbons Chen 1996, 1994 ;BuAbbas et al 1994 ;Apostolides et al 1996 ;Stavric et al 1996). At least two mechanisms appear to mediate the antimutagenic e †ects of green tea (Bu-Abbas et al 1994) : inhibition of the cytochrome P450-dependent bioactivation of chemical carcinogens and, to a lesser degree, scavenging of the reactive intermediates, thus preventing them from interacting with DNA.…”

Role of tea catechins in prevention of aging and age-related disorders

“…Wang (Wang et al, 1989) suggested green tea polyphenols have a significant anti-skin tumour initiating activity when tested against polycyclic aromatic hydrocarbons in mice. Catechins possess antimutagenic activities (Bu-Abbas et al, 1994), and anti-genotoxic effects (Sugisawa et al, 2004), induce apoptosis in cancer cells (Hayakawa et al, 2001), and inhibit angiogenesis (Jung et al, 2001) that makes them useful as anti-carcinogenic compounds. In epithelial tumours, the epidermal growth factor receptor (EGFR) is highly expressed and is inhibited by EGCG (Masuda et al, 2001;Shimizu et al, 2005).…”