Inhibitory effects of (-)-epigallocatechin gallate on the mutation,DNA strand cleavage,and DNA adduct formation by heterocyclic amines |
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| Authors: | Arimoto-Kobayashi Sakae Inada Naomi Sato Yasuko Sugiyama Chitose Okamoto Keinosuke Hayatsu Hikoya Negishi Tomoe |
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| Institution: | Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima, Okayama 700-8530, Japan. arimoto@cc.okayama-u.ac.jp |
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| Abstract: | Green tea is known to be a potential chemopreventive agent against cancer. In this study, we investigated the inhibitory activities of tea extracts, and in particular the polyphenolic component (-)-epigallocatechin gallate (EGCG), against heterocyclic amine-induced genotoxicity. The tea extracts displayed inhibition of 2-hydroxyamino-6-methyldipyrido1,2-a,3',2'-d]imidazole (Glu-P-1(NHOH))-induced mutagenicity. This inhibition can be accounted for by the presence of EGCG in the extracts. The mutagenic effect of Glu-P-1(NHOH), which induces single-strand cleavage in supercoiled circular DNA under neutral conditions, was inhibited by EGCG. Using the Drosophila repair test, a test for gross DNA damage, and DNA adduct detection by (32)P-postlabeling, we showed that EGCG prevented 2-amino-3,8-dimethylimidazo4,5-f]quinoline-induced DNA damage and adduct formation in insect DNA. EGCG was found to accelerate the degradation of Glu-P-1(NHOH) in vitro. This observation suggested that the inhibition by EGCG is associated with an accelerated degradation of metabolically activated heterocyclic amines. |
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