Long-term exposure of K562 cells to benzene metabolites inhibited erythroid differentiation and elevated methylation in erythroid specific genes
Long-term exposure of K562 cells to benzene metabolites inhibited erythroid differentiation and elevated methylation in erythroid specific genes
复制标题
K562细胞长期暴露于苯代谢物会抑制红系分化并导致红系特异性基因甲基化升高
DOI：
10.1039/c6tx00143b
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发表时间：
2016
影响因子：
2.1
通讯作者：
Yi Z. C.
中科院分区：
文献类型：
--
作者：
Tang K. Y.;Yu C. H.;Jiang L.;Gong M.;Liu W. J.;Wang Y.;Cui N. X.;Song W.;Sun Y.;Yi Z. C.
Benzene is a common occupational hazard and a widespread environmental pollutant. Previous studies have revealed that 72 h exposure to benzene metabolites inhibited hemin-induced erythroid differentiation of K562 cells accompanied with elevated methylation in erythroid specific genes. However, little is known about the effects of long-term and low-dose benzene metabolite exposure. In this study, to elucidate the effects of long-term benzene metabolite exposure on erythroid differentiation, K562 cells were treated with low-concentration phenol, hydroquinone and 1,2,4-benzenetriol for at least 3 weeks. After exposure of K562 cells to benzene metabolites, hemin-induced hemoglobin synthesis declined in a concentration- and time-dependent manner, and the hemin-induced expressions of α-, β- and γ-globin genes and heme synthesis enzyme porphobilinogen deaminase were significantly suppressed. Furthermore, when K562 cells were continuously cultured without benzene metabolites for another 20 days after exposure to benzene metabolites for 4 weeks, the decreased erythroid differentiation capabilities still remained stable in hydroquinone- and 1,2,4-benzenetriol-exposed cells, but showed a slow increase in phenol-exposed K562 cells. In addition, methyltransferase inhibitor 5-aza-2′-deoxycytidine significantly blocked benzene metabolites inhibiting hemoglobin synthesis and expression of erythroid genes. Quantitative MassARRAY methylation analysis also confirmed that the exposure to benzene metabolites increased DNA methylation levels at several CpG sites in several erythroid-specific genes and their far-upstream regulatory elements. These results demonstrated that long-term and low-dose exposure to benzene metabolites inhibited the hemin-induced erythroid differentiation of K562 cells, in which DNA methylation played a role through the suppression of erythroid specific genes.
