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女性献血者的雌激素状态和儿茶酚-O-甲基转移酶(COMT)基因型会影响地中海植物提取物对过氧化氢诱导的淋巴细胞DNA损伤的保护能力。

The estrogenic status and the COMT genotype of female blood donors influence the protective ability of the Mediterranean plant extracts against the hydrogen peroxide-induced DNA damage in lymphocytes.

作者信息

Kapiszewska M, Zajac G, Kalemba M, Sołtys E

机构信息

Department of General Biochemistry, Faculty of Biotechnology, Jagiellonian University, Kraków, Poland.

出版信息

J Physiol Pharmacol. 2005 Mar;56 Suppl 1:199-217.

Abstract

The extent of oxidative DNA damage in lymphocytes can be used as a biomarker of the level of oxidative stress in the body. The comet assay has been widely used to measure such damage. The aim of our study was to evaluate: i) the extent of the oxidative DNA damage in lymphocytes isolated from blood of female donors taken in early and late follicular phases [low (LE) and high (HE) concentration of 17beta-estradiol, respectively], ii) the susceptibility of these lymphocytes to hydrogen peroxide exposure, and iii) the protective ability of five plant extracts against the hydrogen peroxide-induced DNA damage. The effect of the catechol-O-methytransferase genotype (wild COMT H/H and mutated homozygote COMT L/L) of female donors was also analyzed. The amount of endogenous DNA damage was higher in HE lymphocytes as compared with LE ones, independently of the genotype. When lymphocytes were stratified by COMT genotype, the level of DNA damage was higher in L/L donors. The protective effect of pretreatment with plant extracts (1 and 10 micro g/ml for 1 h) against the H(2)O(2) (25 microM, 5 min. at 4 degrees C)-induced oxidative DNA damage was observed only in H/H HE lymphocytes. In contrary, the plant extract pre-incubation enhanced the DNA damage in L/L HE lymphocytes. The plant extracts alone did not induce the DNA damage. The results showed that concentration of the circulating 17beta-estradiol influenced the extent of endogenous oxidative DNA damage while the beneficial or hazardous effects of the plant extracts might depend on the COMT genotype and the estrogen level.

摘要

淋巴细胞中氧化性DNA损伤的程度可作为体内氧化应激水平的生物标志物。彗星试验已被广泛用于测量此类损伤。我们研究的目的是评估:i)从处于卵泡期早期和晚期的女性献血者血液中分离出的淋巴细胞中氧化性DNA损伤的程度[分别为低(LE)和高(HE)浓度的17β-雌二醇],ii)这些淋巴细胞对过氧化氢暴露的敏感性,以及iii)五种植物提取物对过氧化氢诱导的DNA损伤的保护能力。还分析了女性献血者儿茶酚-O-甲基转移酶基因型(野生型COMT H/H和突变纯合子COMT L/L)的影响。与LE淋巴细胞相比,HE淋巴细胞中内源性DNA损伤的量更高,与基因型无关。当按COMT基因型对淋巴细胞进行分层时,L/L献血者的DNA损伤水平更高。仅在H/H HE淋巴细胞中观察到用植物提取物(1和10μg/ml,处理1小时)预处理对H₂O₂(25μM,4℃下处理5分钟)诱导的氧化性DNA损伤具有保护作用。相反,植物提取物预孵育增强了L/L HE淋巴细胞中的DNA损伤。植物提取物单独使用不会诱导DNA损伤。结果表明,循环中的17β-雌二醇浓度影响内源性氧化性DNA损伤的程度,而植物提取物的有益或有害作用可能取决于COMT基因型和雌激素水平。

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