Prooxidant activity of flavonoids: Copper-dependent strand breaks and the formation of 8-hydroxy-2'-deoxyguanosine in DNA

被引:83
作者
Yoshino, M
Haneda, M
Naruse, M [1 ]
Murakami, K
机构
[1] Aichi Med Univ, Dept Biochem, Nagakute, Aichi 4801195, Japan
[2] Aichi Med Univ, Cent Res Labs, Nagakute, Aichi 4801195, Japan
关键词
flavonoid; 8-hydroxy-2'-deoxyguanosine; DNA; copper; hydroxyl radical; DNA strand breaks;
D O I
10.1006/mgme.1999.2901
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The naturally occurring flavonoids caused strand scission of DNA in the presence of copper ion. Flavonoids such as myricetin, baicalein, and quercetin as well as ascorbic acid cleaved plasmid pBR322 DNA and calf thymus DNA potently. Addition of catalase protected DNA from the strand breaks caused by flavonoids. Treatment of calf thymus DNA with these flavonoids or ascorbate plus copper produced 8-hydroxy-2'-deoxyguanosine. Cuprous ion reduced by flavonoids and ascorbic acid may play a key role in the oxidative cleavage of DNA and the formation of base adduct. Mutagenic and carcinogenic action of flavonoids may be explained by the prooxidant effects of the compounds. (C) 1999 Academic Press.
引用
收藏
页码:468 / 472
页数:5
相关论文
共 23 条
[1]   OXIDANTS, ANTIOXIDANTS, AND THE DEGENERATIVE DISEASES OF AGING [J].
AMES, BN ;
SHIGENAGA, MK ;
HAGEN, TM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (17) :7915-7922
[2]   A REVIEW OF THE GENETIC-EFFECTS OF NATURALLY-OCCURRING FLAVONOIDS, ANTHRAQUINONES AND RELATED-COMPOUNDS [J].
BROWN, JP .
MUTATION RESEARCH, 1980, 75 (03) :243-277
[3]   DAMAGE TO THE DNA BASES IN MAMMALIAN CHROMATIN BY HYDROGEN-PEROXIDE IN THE PRESENCE OF FERRIC AND CUPRIC IONS [J].
DIZDAROGLU, M ;
RAO, G ;
HALLIWELL, B ;
GAJEWSKI, E .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1991, 285 (02) :317-324
[4]   THE ROLE OF 8-HYDROXYGUANINE IN CARCINOGENESIS [J].
FLOYD, RA .
CARCINOGENESIS, 1990, 11 (09) :1447-1450
[5]   MODIFICATION OF DNA BASES IN MAMMALIAN CHROMATIN BY RADIATION-GENERATED FREE-RADICALS [J].
GAJEWSKI, E ;
RAO, G ;
NACKERDIEN, Z ;
DIZDAROGLU, M .
BIOCHEMISTRY, 1990, 29 (34) :7876-7882
[6]  
HALLIWELL B, 1992, J LAB CLIN MED, V119, P598
[7]   FLAVONOIDS, A CLASS OF NATURAL-PRODUCTS OF HIGH PHARMACOLOGICAL POTENCY [J].
HAVSTEEN, B .
BIOCHEMICAL PHARMACOLOGY, 1983, 32 (07) :1141-1148
[8]   EVIDENCE FOR THE ACCUMULATION OF OXIDATIVE STRESS DURING CELLULAR AGING OF HUMAN-DIPLOID FIBROBLASTS [J].
HOMMA, Y ;
TSUNODA, M ;
KASAI, H .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1994, 203 (02) :1063-1068
[9]  
KAGAWA TF, 1991, J BIOL CHEM, V266, P20175
[10]   Quantitation of 8-oxoguanine and strand breaks produced by four oxidizing agents [J].
Kennedy, LJ ;
Moore, K ;
Caulfield, JL ;
Tannenbaum, SR ;
Dedon, PC .
CHEMICAL RESEARCH IN TOXICOLOGY, 1997, 10 (04) :386-392