Galloylated catechins as potent inhibitors of hypochlorous acid-induced DNA damage.
Hypochlorous acid (HOCl), a strong oxidant derived from myeloperoxidase in neutrophils and macrophages, can chlorinate DNA bases at the site of inflammation. Because little is known about the protective role of natural antioxidants, such as polyphenols, for the myeloperoxidase-derived DNA damage, we screened the inhibitory effects of various phenolic antioxidants on the chlorination of the 2'-deoxycytidine residue by HOCl in vitro and found that green tea catechins, especially (-)-epicatechin gallate (ECg) and (-)-epigallocatechin gallate (EGCg), significantly inhibited the chlorination. These catechins also reduced nucleoside- and taurine-chloramines, which can induce secondary oxidative damage, into their native forms. Mass spectrometric and nuclear magnetic resonance analyses showed that ECg and EGCg can effectively scavenge HOCl and/or chloramine species resulting in the formation of mono- and dichlorinated ECg and EGCg. Using the HL-60 human leukemia cell line, it was found that ECg could efficiently accumulate in the cells. Immunocytometric analyses using antihalogenated 2'-deoxycytidine antibody showed that pretreatment of cells with ECg inhibited the HOCl-induced immunofluorescence. In addition, the chlorinated ECg derivatives were detected in the HOCl-treated HL-60 cells. These results showed that green tea catechins, especially 3-galloylated catechins, may be the plausible candidate for the prevention of inflammation-derived DNA damage and perhaps carcinogenesis.
Kawai
Yoshichika
Y
Laboratory of Food Biodynamics, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan. y-kawai@nutr.med.tokushima-u.ac.jp
Matsui
Yuri
Y
Kondo
Hajime
H
Morinaga
Hiroshi
H
Uchida
Koji
K
Miyoshi
Noriyuki
N
Nakamura
Yoshimasa
Y
Osawa
Toshihiko
T
D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000737:chemistry / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D016166:Free Radical Scavengers / Q000378:metabolism / Q000494:pharmacology*; D018922:HL-60 Cells; D054879:Halogenation; D006801:Humans; D006997:Hypochlorous Acid / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000633:toxicity*; D016877:Oxidants / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000633:toxicity*; D010936:Plant Extracts / Q000378:metabolism / Q000494:pharmacology; D013662:Tea / Q000737:chemistry
D004273:DNA, Neoplasm; D016166:Free Radical Scavengers; D016877:Oxidants; D010936:Plant Extracts; D013662:Tea; D006997:Hypochlorous Acid; D002392:Catechin; D004247:DNA; C427203:calf thymus DNA; C062669:epicatechin gallate; C057580:gallocatechol