Catechins induce oxidative damage to cellular and isolated DNA through the generation of reactive oxygen species.
Green tea catechins have antimutagenic and anticarcinogenic activities. On the other hand, several epidemiological studies have indicated significant positive relationship between green tea consumption and cancer. Catechins enhance colon carcinogenesis in rats initiated with chemical carcinogen. To clarify the mechanism underlying the potential carcinogenicity, we investigated the DNA-damaging ability of catechins in human cultured cells. Catechin increased the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a characteristic oxidative DNA lesion, in human leukemia cell line HL-60 but not in HP100, a hydrogen peroxide (H2O2)-resistant cell line derived from HL-60. The catechin-induced formation of 8-oxodG in HL-60 cells significantly decreased by bathocuproine. Furthermore, we investigated DNA damage and its site-specificity induced by catechins, using 32P-labeled DNA fragments. Catechin and epicatechin induced extensive DNA damage in the presence of Cu(II). Catechin caused piperidine-labile sites at thymine and cytosine residues in the presence of Cu(II). Catalase and bathocuproine inhibited the DNA damage, indicating the involvement of H2O2 and Cu(I). NADH enhanced catechins plus Cu(II)-induced 8-oxodG formation in calf thymus DNA, suggesting the redox cycle between catechins and their corresponding quinones, the oxidized forms of catechins. The DNA-damaging ability of epicatechin is stronger than that of catechin, possibly due to the greater turnover frequency of the redox cycle. The difference in their redox properties could be explained by their redox potentials estimated form an ab initio molecular orbital calculation. The present study demonstrated that catechins could induce metal-dependent H2O2 generation during the redox reactions and subsequently damage to cellular and isolated DNA. Therefore, it is reasonably considered that green tea catechins may have the dual function of anticarcinogenic and carcinogenic potentials.
Department of Environmental and Molecular Medicine, Mie University School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan.
Shinji
S
Oikawa
Ayako
A
Furukawaa
Hideyuki
H
Asada
Kazutaka
K
Hirakawa
Shosuke
S
Kawanishi
D000818:Animals; D002374:Catalase / Q000378:metabolism; D002392:Catechin / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D003300:Copper / Q000737:chemistry; D003596:Cytosine / Q000737:chemistry; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004249:DNA Damage; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007202:Indicators and Reagents / Q000494:pharmacology; D008956:Models, Chemical; D018384:Oxidative Stress; D010618:Phenanthrolines / Q000494:pharmacology; D010710:Phosphates / Q000494:pharmacology; D011809:Quinones / Q000737:chemistry; D017382:Reactive Oxygen Species; D013941:Thymine / Q000737:chemistry; D013950:Thymus Gland / Q000378:metabolism; D014466:Ultraviolet Rays
D007202:Indicators and Reagents; D010618:Phenanthrolines; D010710:Phosphates; D011809:Quinones; D017382:Reactive Oxygen Species; D003300:Copper; D003596:Cytosine; D002392:Catechin; D004247:DNA; C002478:bathocuproine; D006861:Hydrogen Peroxide; D002374:Catalase; D013941:Thymine; C018279:sodium phosphate