title: [Effects of trichloroethylene toxicity on normal human liver cells and hepatocytes with CYP2E1 gene overexpression].
abstract: OBJECTIVE
  To investigate the effects of trichloroethylene (TCE) toxicity on the normal human liver cells (L02 cells) and hepatocytes with CYP2E1 gene overexpression which was constructed through molecular cloning technology in our laboratory, then to explore the roles of CYP2E1 gene in TCE toxicity.
  
  
  METHODS
  L02 cells and hepatocytes with CYP2E1 overexpression were treated with various doses of TCE (0,0.25, 0.5, 1.0, 2.0, 4.0 mmol/L) for 12h, the expression of apoptosis genes (Bcl-2, Caspase-3, Caspase-8, Caspase-9) and oncogenes (c-fos, c-myc, k-ras, p53) were determined by real-time fluorescent PCR.
  
  
  RESULTS
  Bcl-2 mRNA expression levels increased significantly in normal liver cells and CYP2E1-overexpressing cells after TCE treatment, Bcl-2 levels were 20%∼50%higher in CYP2E1-overexpressing cells than in L02 liver cells at doses of 0.25∼2.0 mmol/L TCE. Caspase-3, Caspase-8 and caspase-9 mRNA expression increased by 30%∼600% in CYP2E1-overexpressing cells at doses of 0.5∼4.0 mmol/L TCE when compared with L02 cells (P < 0.01). Additionally, c-fos, k-ras and c-myc mRNA expression levels were 25%∼120% higher in CYP2E1-overexpressing cells than in L02 cells (P < 0.01), p53 mRNA expression levels were lower 10%∼50% in CYP2E1-overexpressing cells than in L02 cells (P < 0.05 or P < 0.01).
  
  
  CONCLUSIONS
  There were significant differences for apoptosis gene and oncogene expression levels between normal liver cells and CYP2E1-overexpressing cells after they were treated with TCE, these findings indicated that CYP2E1 might play an important role in TCE metabolism in vivo.
authors.affiliation: Shenzhen Center for Disease Control and Prevention, Shenzhen key laboratory of health toxicology, Shenzhen key laboratory of modern toxicology, Shenzhen, Guangdong 518055, China.
authors.forename: Xinyun
authors.initials: X
authors.lastname: Xu
authors.forename: Kanlang
authors.initials: K
authors.lastname: Mao
authors.forename: Jianhui
authors.initials: J
authors.lastname: Yuan
authors.forename: Desheng
authors.initials: D
authors.lastname: Wu
authors.forename: Haiyan
authors.initials: H
authors.lastname: Huang
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Qin
authors.forename: Qin
authors.initials: Q
authors.lastname: Tan
mesh_terms: D051017:Apoptosis Regulatory Proteins; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D015870:Gene Expression; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D008099:Liver; D011519:Proto-Oncogenes / Q000235:genetics; D012333:RNA, Messenger; D014241:Trichloroethylene / Q000633:toxicity*
chemical_list: D051017:Apoptosis Regulatory Proteins; D012333:RNA, Messenger; D014241:Trichloroethylene; D019392:Cytochrome P-450 CYP2E1; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9