三氯乙烯对B6C3F1雄性小鼠肝脏和肾脏中细胞增殖相关基因表达和DNA甲基化的影响

doi:10.3969/j.issn.1004-616x.2015.03.011

Abstract

Abstract:

OBJECTIVE: Trichloroethylene (TCE), a common industrial contaminant in the environment, could induce hepatocellular carcinoma but not kidney cancer in mice. This study aimed to understand the molecular mechanisms of TCE hepatocarcinogenicity by examining the effect of TCE on proliferation-related mRNA expression and DNA methylation in mouse liver and kidney. METHODS:B6C3F1 male mice aged six weeks were randomly divided into 3 groups, with 4 mice in each group. Mice were fed with TCE at 0, 500 and 1 000 mg/kg for 5 days. Using qPCR, we examined the mRNA expression of genes involved in cell proliferation and in the regulation of DNA methylation in TCE-exposed mouse liver and kidney. The promoter methylation status of Cdkn1a and the DNA methylation level of repetitive sequences were detected by combined bisulfite restriction analysis. RESULTS:Compared with control, TCE increased the mRNA expression of Cdkn1a, Jun and Mki67 in a dose-dependent manner in mouse liver. Moreover, in mouse treated with TCE at 1 000 mg/kg, the mRNA expression of a number of key DNA methylation regulation genes including Dnmt3a, Dnmt3b and Tet2 were down-regulated, while the mRNA expression level of Uhrf1 was up-regulated (all P<0.05). TCE also induced hypomethylation of the promoter region of Cdkn1a in mouse hepatocytes. However, TCE should no detectable effects on mRNA expression and DNA methylation in mouse kidney. CONCLUSION:Alterations in the mRNA expression of proliferation-related genes and DNA methylation changes might be crucial to TCE-induced hepatocarcinogenesis in mice.

Key words: trichloroethylene, mRNA, DNA methylation, hepatocellular carcinoma, cell proliferation

CLC Number:

R114

CHEN Jiahong, ZHANG Hang, LAI Yi, JIANG Yan, CHEN Tao. Cell proliferation-related mRNA expression and DNA methylation changes induced by trichloroethylene in the liver and kidney of B6C3F1 male mice[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2015, 27(3): 211-215.

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Cell proliferation-related mRNA expression and DNA methylation changes induced by trichloroethylene in the liver and kidney of B6C3F1 male mice

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