title: [Effects of long term and low dose Di- (2-ethylhexyl) phthalate exposure on global genome DNA methylation in HePG2 cells].
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) -methyltransferase 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 HePG2 cells were down-regulated along with the increasing of DEHP exposure level (15.0, 150.0 μmol/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.
  
  
  CONCLUSIONS
  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.
authors: Key Laboratory of Genetics & Molecular Medicine of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China.
authors: Z Q
authors: ZQ
authors: Lyu
authors: X
authors: X
authors: Xie
authors: Y B
authors: YB
authors: Ke
mesh_terms: D019175:DNA Methylation; D015894:Genome, Human; D056945:Hep G2 Cells; D006801:Humans; D010795:Phthalic Acids
chemical_list: D010795:Phthalic Acids; C032279:phthalic acid