Effects of long term and low dose Di-(2-ethylhexyl) phthalate exposure on global genome DNA methylation in HePG2 cells
10.3760/cma.j.issn.1001-9391.2016.05.008
- VernacularTitle:邻苯二甲酸二(2-乙基)己酯长期低剂量染毒对HepG2细胞DNA甲基化的影响
- Author:
Ziquan LYU
1
,
2
;
Xing XIE
;
Yuebin KE
Author Information
1. 430030 武汉,华中科技大学同济医学院公共卫生学院,教育部环境与健康重点实验室
2. 深圳市疾病预防控制中心,深圳市现代医学分子生物重点实验室
- Keywords:
Di-(2-ethylhexyl) phthalate (DEHP);
DNA (cytosine-5)-methyltransferase 1;
DNA methylation
- From:
Chinese Journal of Industrial Hygiene and Occupational Diseases
2016;34(5):346-351
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the potential effects of long-term and low-dose Di-(2-ethylhexyl)phthalate (DEHP) exposure on whole genome DNA methylation status and cytotoxicity of HePG2 cells.Methods HePG2 cells were exposed to 1.5、15.0 and 150.0 μmol/L DEHP for 24 hours,after continuous exposure for 20 generations,mRNA and protein expression level of DNA (cytosine-5)-methyhransferase 1(DNMT 1),whole genome DNA methylation,cell apoptosis levels and cell cycle were determined in both DEHP exposed cells and control cells.Results After DEHP exposure,the mRNA and protein expression levels of DNMT 1 were decreased significantly (P＜0.05 or P＜0.01).The genome DNA methylation levels of HePG2cells were down-regulated along with the increasing of DEHP exposure level (15.0,150.0 μμmol/L,P＜0.05 and P＜0.01).In term of cell apoptosis rates,only the late-stage cell apoptosis rates of the highest DEHP dosage group (150.0 μmol/L DEHP) were observed to have a significant increase (P＜0.05).There were no significant alterations in term of cell cycle.Conclusion After long term and low dose DEHP exposure,the whole genome DNA methylation levels of HePG2 cells were down regulated obviously,which might be one of the most important toxic mechanism of DEHP to induce pathophysiologic changes.Meanwhile,a certain content of cell apoptosis were observed in highest dosage group of DEHP exposure,which showed cytotoxicty of DEHP.However,there are no significant effects of DEHP exposure on cell cycles.
