The relationship between 8-oxo-7,8-dihydro-2′-deoxyguanosine level and extent of cytosine methylation in leukocytes DNA of healthy subjects and in patients with colon adenomas and carcinomas
The relationship between 8-oxo-7,8-dihydro-2′-deoxyguanosine level and extent of cytosine methylation in leukocytes DNA of healthy subjects and in patients with colon adenomas and carcinomas
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DOI：
10.1016/j.mrfmmm.2007.12.013
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发表时间：
2008-04-02
影响因子：
2.3
通讯作者：
Olinski, Ryszard
中科院分区：
文献类型：
--
作者：
Guz, Jolanta;Foksinski, Marek;Olinski, Ryszard
很长一段时间以来，人们都知道DNA低甲基化发生在许多人类癌症和癌前病变中。然而，低甲基化的机制在很大程度上是未知的。内源性8-氧-7,8-二氢鸟嘌呤（8-氧- gua）水平可能与邻近胞嘧啶的异常DNA甲基化有关，并以这种方式影响致癌作用。因此，本研究的目的是评估8-氧-7,8-二氢-2'-脱氧鸟苷(8-氧-7,8-二氢-2'-脱氧鸟苷（8-氧）背景水平与健康受试者（n = 105）以及结肠腺瘤（n = 39）和癌（n = 50）患者白细胞DNA中5-甲基胞嘧啶含量之间的可能联系。我们的结果显示，从健康供体白细胞分离的DNA中8-oxodG的背景水平与5-甲基胞嘧啶含量之间存在统计学上显著的负相关（r = -0.3436, p=0.0003）。结肠腺瘤和癌患者白细胞DNA中5-甲基胞嘧啶的平均含量明显低于健康人，8-氧合g的平均含量明显高于健康人。5-甲基胞嘧啶的平均值为：健康受试者3.59 +/- 0.173%，腺瘤患者3.38 +/- 0.128%，结肠癌患者3.40 +/- 0.208%。DNA中8-oxodG的平均值分别为：4.67 +/- 1.276、5.72 +/- 1.787、5.76 +/- 1.8848-oxodG / 10(6) dG分子。与配对受试者的白细胞相比，来自受影响组织（结肠）的DNA的胞嘧啶甲基化显著减少约10%。我们的工作提供了第一个体内证据，表明DNA中8-oxodG水平的增加不仅可能通过修饰碱基的错配/致突变潜力导致致癌，还可能通过其通过影响DNA甲基化影响基因表达的能力导致致癌。(C) 2008 Elsevier B.V.版权所有
It has been known for a long time that DNA hypomethylation occurs in many human cancers and precancerous conditions. However, the mechanisms of hypomethylation are largely unknown. It is possible that endogenous 8-oxo-7,8-dihydroguanine (8-oxoGua) level may be linked to aberrant DNA methylation of adjacent cytosine and in this way influences carcinogenesis. Therefore, the aim of the present study was to assess a possible link between 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) background level and 5-methylcytosine content in DNA from human leukocytes of healthy subjects (n = 105) as well as in patients with colon adenomas (n = 39) and carcinomas (n = 50).Our results demonstrated statistically significant negative correlation between background level of 8-oxodG and 5-methylcytosine content in DNA isolated from leukocytes of healthy donors (r = -0.3436, p=0.0003). The mean content of 5-methylcytosine was significantly lower, while 8-oxodG level was significantly higher in leukocytes DNA of patients with colon adenomas and carcinomas in comparison with healthy subjects. The mean values for 5-methylcytosine were: 3.59 +/- 0.173% (healthy subjects), 3.38 +/- 0.128% (patients with adenomas), 3.40 +/- 0.208% (colon cancer patients). The mean values of 8-oxodG in DNA were, respectively: 4.67 +/- 1.276, 5.72 +/- 1.787, 5.76 +/- 1.8848-oxodG per 10(6) dG molecules. DNA from affected tissue (colon) suffered from significant, about 10% reduction in cytosine methylation in comparison with leukocytes of the paired subjects.Our work provides the first in vivo evidence suggesting that increased levels of 8-oxodG in DNA may lead to carcinogenesis not only via mispair/mutagenic potential of the modified base but also through its ability to influence gene expression by affecting DNA methylation. (C) 2008 Elsevier B.V. All rights reserved.