Changes in DNA methylation of erythroid-specific genes in K562 cells exposed to phenol and hydroquinone
Changes in DNA methylation of erythroid-specific genes in K562 cells exposed to phenol and hydroquinone
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接触苯酚和氢醌的 K562 细胞中红系特异性基因 DNA 甲基化的变化
DOI：
10.1016/j.tox.2013.08.007
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发表时间：
2013-10-04
期刊：
影响因子：
4.5
通讯作者：
Yi, Zong-Chun
中科院分区：
文献类型：
--
作者：
Li, Yang;Wu, Xiao-Rong;Yi, Zong-Chun
苯是一种常见的职业危害，也是一种广泛存在的污染物。苯的代谢产物在其对造血系统的毒性中起重要作用，但苯代谢产物如何影响红细胞生成的研究却知之甚少。我们以前的研究表明，苯的代谢产物，包括苯酚和氢醌，抑制氯化血红素诱导的K562细胞的红系分化。为了阐明DNA甲基化在苯代谢物诱导的红系细胞分化抑制中的作用，本研究考察了DNA甲基化酶抑制剂5-氮杂-2 '-脱氧胞苷（5-aza-2'-deoxycytidine，5-aza-2 '-deoxycytidine，5-aza-2'-deoxycytidine）是否能抑制苯代谢物诱导的红系细胞分化。（5-aza-CdR）能够阻止苯代谢物抑制氯化血红素诱导的K562细胞红系分化，采用Quantitative MassARRAY甲基化分析平台分析苯代谢物处理K562细胞后红系特异性基因甲基化水平。发现用5-aza-CdR处理K562细胞完全阻止苯酚和氢醌抑制氯化血红素诱导的血红蛋白合成和氯化血红素诱导的红系特异性基因的表达，包括α-和β-珠蛋白、红系胆色素原脱氨酶和加塔结合蛋白1（加塔-1）。结果表明，苯代谢产物可引起红系细胞特异性基因的甲基化水平升高，包括α-珠蛋白基因和α-簇HS 40元件、β-珠蛋白基因和β-珠蛋白基因簇LCR中的HS核心序列、红系细胞胆色素原脱氨酶基因和加塔-1基因。这些结果表明，DNA甲基化通过下调红系相关基因的转录，在苯代谢产物抑制氯化血红素诱导的K562细胞向红系分化中发挥作用。(C)2013爱思唯尔爱尔兰有限公司版权所有。
Benzene is a common occupational hazard as well as a widespread pollutant. Its metabolites play important roles in its toxicity to the hematopoietic system, but little is known about how benzene metabolites affect erythropoiesis. Our previous study demonstrated that benzene metabolites, including phenol and hydroquinone, inhibited hemin-induced erythroid differentiation of K562 cells. In present study, to elucidate the role of DNA methylation in benzene metabolites-induced inhibition on erythroid differentiation, it was investigated whether DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-aza-CdR), was able to prevent benzene metabolites inhibiting hemin-induced erythroid differentiation in K562 cells, and the methylation levels of erythroid-specific genes in benzene metabolites-treated K562 cells were analyzed by Quantitative MassARRAY methylation analysis platform. It was found that treatment of K562 cells with 5-aza-CdR completely prevented phenol and hydroquinone inhibiting hemin-induced hemoglobin synthesis and hemin-induced expression of erythroid specific genes, including alpha- and beta-globin, erythroid porphobilinogen deaminase and GATA binding protein 1 (GATA-1). Consistently, the exposure to benzene metabolites caused an increase in DNA methylation levels at a few CpG sites in some erythroid specific genes, including alpha-globin gene and alpha-cluster HS40 element, beta-globin gene and HS core sequence in LCR of beta-globin gene cluster, erythroid porphobilinogen deaminase gene, and GATA-1 gene. These results indicated that DNA methylation played a role in benzene metabolites inhibiting hemin-induced erythroid differentiation of K562 cells via down-regulating transcription of some erythroid related genes. (C) 2013 Elsevier Ireland Ltd. All rights reserved.