Methylation of PARP-1 promoter involved in the regulation of benzene-induced decrease of PARP-1 mRNA expression
Methylation of PARP-1 promoter involved in the regulation of benzene-induced decrease of PARP-1 mRNA expression
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DOI：
10.1016/j.toxlet.2010.03.005
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发表时间：
2010-06-02
影响因子：
3.5
通讯作者：
Tian, Lin
中科院分区：
文献类型：
--
作者：
Gao, Ai;Zuo, Xin;Tian, Lin
苯是一种确定的血液毒性致癌物，可导致白血病。DNA损伤和修复能力障碍是苯致白血病的重要机制。DNA甲基转移酶抑制剂5-氮杂-2 '-脱氧胞苷（5-aza）和组蛋白去乙酰化酶抑制剂曲马斯他丁A（TSA）是两类关键的表观遗传修饰试剂。苯可降低损伤修复关键基因聚ADP核糖聚合酶-1（PARP-1）的mRNA表达。然而，表观遗传修饰对苯诱导的低PARP-1表达的影响尚未报道。在这项研究中，淋巴母细胞系F32与苯孵育，然后进一步用5-aza和TSA单独或联合处理。采用逆转录-聚合酶链反应（RT-PCR）和甲基化特异性PCR（methylation-specific PCR）检测PARP-1 mRNA表达和甲基化状态。结果显示，与对照组相比，苯处理的细胞中PARP-1 mRNA表达显著降低，同时PARP-1甲基化水平明显升高。此外，在表观遗传抑制剂5-aza和TSA单独或联合治疗后，PARP-1 mRNA表达恢复，PARP-1甲基化水平也降低。PARP-1基因启动子甲基化可能参与了苯诱导的PARP-1 mRNA表达下降的调控。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Benzene is an established hematotoxic carcinogen which can cause leukemia. DNA damage and disorder of repair capacity are the crucial mechanisms in leukemogenesis of benzene. DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-aza) and histone deacetylase inhibitor, trichostatin A (TSA) are two kinds of key epigenetic modification reagents. The mRNA expression of poly(ADP-ribose) polymerases-1 (PARP-1), a pivotal repair gene, has been decreased by benzene. However, the effect of epigenetic modification on benzene-induced low PARP-1 expression has not been reported. In this study, lymphoblastoid cell line F32 was incubated by benzene and then further treated with 5-aza and TSA, alone or in combination. The reverse transcription-polymerase chain reaction and methylation-specific PCR were performed to examine the mRNA expression and methylation status of PARP-1, respectively. Results showed a dramatic decrease of PARP-1 mRNA expression and a simultaneously obvious increase in the level of PARP-1 methylation in benzene-treated cells compared to the control. Further, the PARP-1 mRNA expression was restored and the level of PARP-1 methylation was also reduced following epigenetic inhibitors, 5-aza and TSA, alone or in combination treatments. Taken together, methylation of PARP-1 promoter might be involved in the regulation of benzene-induced decrease of PARP-1 mRNA expression. (C) 2010 Elsevier Ireland Ltd. All rights reserved.