期刊
TOXICOLOGY LETTERS
卷 209, 期 3, 页码 239-245出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2011.12.020
关键词
DNA methylation; Hydroquinone; DNMT; MPL; TK6 cells
类别
资金
- National Natural Science Foundation of China [30972500]
- Natural Science Foundation of Guangdong Province [7301507]
- Dongguan Bureau of Science and Technology, China [201010815206]
Hydroquinone (HQ), one of the most important metabolites derived from benzene, is known to be associated with acute myelogenous leukemia (AML) risk, however, its carcinogenic mechanism remains unclear. In this study, the epigenetic mechanism of HQ exposure was investigated. We characterized the epigenomic response of TK6 cells to HQ exposure, and examined the mRNA expression of DNA methyltransferases (DNMTs) including DNMT1, DNMT3a and DNMT3b, methyl-CpG-binding domain protein 2 (MBD2) and six proto-oncogenes (MPL, RAF1, MYB, MYC, ERBB2 and BRAF). Compared to the control cells, HQ exposure (2.5, 5.0, 10.0 and 20.0 mu M for 48 h) resulted in the decrease of DNMTs and MBD2 expression, the global hypomethylation and increase of MPL at mRNA level. Meanwhile, most of these changes were in dose-dependent manner. Moreover, inhibition of DNMTs induced by 5-aza-2'-deoxycytidine (5-AZA), an identified DNMT inhibitor, caused more induction of MPL expression at mRNA level compared to the HQ(10.0 mu M) pre-treated group. Furthermore, treatment of HQ potentially led to MPL itself hypomethylation (10.0 and 20.0 mu M reduced by 47% and 44%, respectively), further revealing that the activation of proto-oncogene MPL was related to hypomethylation in its DNA sequences. In conclusion, hypomethylation, including global and specific hypomethylation, might be involved in the activation of MPL, and the hypomethylation could be induced by decreased DNMTs in TK6 cells exposed to HQ. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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