Inhibitory effects of (-)-epigallocatechin gallate on the mutation, DNA strand cleavage, and DNA adduct formation by heterocyclic amines.
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-methyldipyrido[1,2-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-dimethylimidazo[4,5-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.
Arimoto-Kobayashi
Sakae
S
Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima, Okayama 700-8530, Japan. arimoto@cc.okayama-u.ac.jp
Inada
Naomi
N
Sato
Yasuko
Y
Sugiyama
Chitose
C
Okamoto
Keinosuke
K
Hayatsu
Hikoya
H
Negishi
Tomoe
T
D000818:Animals; D028241:Camellia sinensis / Q000737:chemistry*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D018736:DNA Adducts / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects*; D004330:Drosophila / Q000235:genetics; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D006358:Hot Temperature; D007093:Imidazoles / Q000494:pharmacology; D016296:Mutagenesis; D009153:Mutagens / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry; D018515:Plant Leaves / Q000737:chemistry; D011804:Quinolines / Q000494:pharmacology
D018736:DNA Adducts; D006571:Heterocyclic Compounds; D007093:Imidazoles; D009153:Mutagens; D010936:Plant Extracts; D011804:Quinolines; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; D002392:Catechin; C045651:epigallocatechin gallate; C036989:2-amino-3,4-dimethylimidazo(4,5-f)quinoline