组蛋白修饰改变在亚砷酸钠毒性效应中的作用研究

doi:10.3969/j.issn.1004-616x.2014.02.002

Abstract

Abstract:

OBJECTIVE: We attempted to investigate the function and regulation mechanism of histone H3 modifications in the toxicity induced by sodium arsenite. METHODS：We constructed histone H3 lysine modified defective cell lines by expressing the site-specific H3 mutation plasmids in HBE cells. MTT assay was used to test the cytotoxicity of these cells when exposed to sodium arsenite. Cytokinesis-block micronucleus (CBMN) assay was conducted to examine the function of H3K4 methylation on the effect of the DNA damage. Meanwhile，the HBE cells were treated with sodium arsenite and the mRNA levels of H3K4 methyltransferases and demethyltransferases and the protein levels of the H3K4 methylation were measured by qRT-PCR and Western blot assay to explore the regulation of H3K4 methylation when exposed to sodium arsenite. RESULTS：We found that the cell vitality was reduced about 60% and the rate of cytokinesis-block micronucleus increased more than 2 times when H3K4 methylation defective HBE cells were exposure to low concentrations (1 μmol/L) of sodium arsenite (P<0.01). The reduction of H3K4 methylation could increase the sensitivity of HBE cells treated with sodium arsenite. We also found that H3K4me2/3 were hypermethylated when exposed to 1 μmol/L sodium arsenite and H3K4 demethylase (lysine-specific demethylase 1，LSD1) was decreased in this process (P<0.05). CONCLUSION：The increased H3K4 methylation might be regulated by reduced LSD1，which may be involved in the cytotoxicity and genotoxity induced by sodium arsenite.

Key words: sodium arsenite, DNA damage, H3K4 metylation, lysine-specific demethylase 1

NIU Lin-mei，ZHANG Zheng-bao，ZENG Xiao-wen，ZHU Xiao-nian，CHEN Wen，LI Diao-chuan. Effect of histone modification in the toxic effects of sodium arsenite[J]. Carcinogenesis, Teratogenesis & Mutagenesis, doi: 10.3969/j.issn.1004-616x.2014.02.002.

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Effect of histone modification in the toxic effects of sodium arsenite

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