Metal-mediated oxidative damage to cellular and isolated DNA by gallic acid, a metabolite of antioxidant propyl gallate
Metal-mediated oxidative damage to cellular and isolated DNA by gallic acid, a metabolite of antioxidant propyl gallate
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DOI：
10.1016/j.mrgentox.2003.11.002
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发表时间：
2004-03-14
影响因子：
1.9
通讯作者：
Kawanishi, S
中科院分区：
文献类型：
--
作者：
Kobayashi, H;Oikawa, S;Kawanishi, S
没食子酸丙酯(PG)被广泛用作食品中的抗氧化剂，对小鼠和大鼠具有致癌作用。PG可增加人白血病细胞株HL-60中8-氧代-7，8-二氢-2‘-脱氧鸟苷(8-oxodG)的含量，但对HL-60衍生的抗过氧化氢(H_2O_2)细胞系HP100无影响。虽然PG对从与人类癌症相关的基因中获得的P-32-5‘末端标记的DNA片段没有或几乎没有损伤，但经酯酶处理后，DNA发生了损伤。对PG与酯酶作用产生的产物进行了高效液相分析，结果表明PG转化为没食子酸(GA)。在Fe(III)、EDTA或Cu(II)存在下，GA以剂量依赖的方式诱导DNA损伤。在Fe(III)络合物如Fe(III)EDTA或Fe(III)ADP的存在下，GA对每个核苷酸都有DNA损伤作用。自由基羟基自由基((OH)-O-)可抑制Fe(III)络合物介导的DNA损伤。清道夫，过氧化氢酶和一种铁络合剂。这些结果表明，Fe(III)络合物介导的DNA损伤主要是由于(OH)-O-引起的。通过芬顿反应产生。在Cu(II)存在下，GA对DNA的损伤发生在胸腺嘧啶和胞嘧啶。虽然(OH)-O-。清道夫对DNA损伤没有预防作用，冰毒对DNA损伤有抑制作用。过氧化氢酶和铜(I)螯合剂可抑制铜(II)介导的DNA损伤。这些结果表明，铜(I)与H_2O_2相互作用形成的活性氧物种参与了DNA损伤。在Cu(II)、Fe(III)EDTA或Fe(III)ADP存在下，GA可增加小牛胸腺DNA中8-oxodG的含量。本研究提示GA引起的金属介导的DNA损伤在PG的致癌作用中起重要作用。(C)2003爱思唯尔B.V.保留所有权利。
Propyl gallate (PG), widely used as an antioxidant in foods, is carcinogenic to mice and rats. PG increased the amount 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, which is hydrogen peroxide (H2O2)-resistant cell line derived from HL-60. Although PG induced no or little damage to P-32-5'-end-labeled DNA fragments obtained from genes that are relevant to human cancer, DNA damage was observed with treatment of esterase. HPLC analysis of the products generated from PG incubated with esterase revealed that PG converted into gallic acid (GA). GA induced DNA damage in a dose-dependent manner in the presence of Fe(III)EDTA or Cu(II). In the presence of Fe(III) complex such as Fe(III)EDTA or Fe(III)ADP, GA caused DNA damage at every nucleotide. Fe(III) complex-mediated DNA damage by GA was inhibited by free hydroxy radical ((OH)-O-.) scavengers, catalase and an iron chelating agent. These results suggested that the Fe(III) complex-mediated DNA damage caused by GA is mainly due to (OH)-O-. generated via the Fenton reaction. In the presence of Cu(II), DNA damage induced by GA occurred at thymine and cytosine. Although (OH)-O-. scavengers did not prevent the DNA damage, methional inhibited the DNA damage. Cu(II)-mediated DNA damage was inhibited by catalase and a Cu(I) chelator. These results indicated that reactive oxygen species formed by the interaction of Cu(I) and H2O2 participates in the DNA damage. GA increased 8-oxodG content in calf thymus DNA in the presence of Cu(II), Fe(III)EDTA or Fe(III)ADP. This study suggested that metal-mediated DNA damage caused by GA plays an important role in the carcinogenicity of PG. (C) 2003 Elsevier B.V. All rights reserved.