Epigallocatechin gallate markedly enhances formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine in the reaction of 2'-deoxyguanosine with hypochlorous acid.
A tea polyphenol, (-)-epigallocatechin gallate (EGCG), which can scavenge a variety of reactive oxygen species, enhances the yield of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) up to 20-fold in the reaction of 2'-deoxyguanosine with hypochlorous acid (HOCl), compared with the reaction without EGCG. Certain concentrations of EGCG inhibited HOCl-mediated oxidation of 2'-deoxyguanosine to 8-oxo-dG to a limited extent, but efficiently inhibited further oxidation of 8-oxo-dG to spiroiminodihydantoin nucleoside, resulting in the accumulation of 8-oxo-dG in the reaction mixture. Conversely, EGCG inhibited dose-dependently an increase in 8-oxo-dG levels in calf thymus DNA incubated with HOCl. However, addition of HOCl to the DNA preoxidized with an oxidant-generating system (CuCl2, ascorbate, H2O2), led to the extensive loss of 8-oxo-dG due to its further oxidation. EGCG effectively inhibited this HOCl-mediated loss of 8-oxo-dG in the oxidized DNA, resulting in an apparent increase in 8-oxo-dG levels in the oxidized DNA, compared with the levels found without EGCG. The conversion of 8-oxo-dG into other oxidized lesions will inevitably affect recognition by DNA repair enzymes as well as the rates of mutations and DNA synthesis. Thus, our results suggest that as a biomarker of oxidative DNA damage, not only 8-oxo-dG but also the products of its further oxidation should be analyzed.
Suzuki
Toshinori
T
International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France.
Nakano
Toshiki
T
Masuda
Mitsuharu
M
Ohshima
Hiroshi
H
D000080242:8-Hydroxy-2'-Deoxyguanosine; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000032:analysis / Q000737:chemistry; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry*; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology*; D005609:Free Radicals / Q000737:chemistry; D006997:Hypochlorous Acid / Q000737:chemistry*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010545:Peroxides / Q000032:analysis / Q000737:chemistry
C057755:DNA hydroperoxide; D016166:Free Radical Scavengers; D005609:Free Radicals; D010545:Peroxides; D006997:Hypochlorous Acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002392:Catechin; D004247:DNA; C427203:calf thymus DNA; C045651:epigallocatechin gallate; D003849:Deoxyguanosine