title: Detection of CYP2E1, a genetic biomarker of susceptibility to benzene metabolism toxicity in immortal human lymphocytes derived from the Han Chinese Population.
abstract: OBJECTIVE
  Cytochrome P450 2E1 (CYP2E1) is an important metabolizing enzyme involved in oxidative stress responses to benzene, a chemical associated with bone marrow toxicity and leukemia. We aimed to identify the CYP2E1 genetic biomarkers of susceptibility to benzene toxicity in support of environmental and occupational exposure prevention, and to test whether a model using immortal human lymphocytes might be an efficient tool for detecting genetic biomarkers.
  
  
  METHODS
  Immortalized human lymphocyte cell lines with independent genotypes on four CYP2E1 SNP sites were induced with 0.01% phenol, a metabolite of benzene. CYP2E1 gene function was evaluated by mRNA expression and enzyme activity. DNA damage was measured by Single-Cell Gel Electrophoresis (SCGE).
  
  
  RESULTS
  Among the four SNPs, cells with rs2070673TT and rs2030920CC showed higher levels of CYP2E1 transcription and enzymatic activity than the other genotypes in the same SNP site. Cells with higher gene expression genotypes also showed higher comet rates compared with lower gene expression genotypes.
  
  
  CONCLUSIONS
  These results suggest that CYP2E1 rs2070673 and rs2030920 might be the genetic biomarkers of susceptibility to benzene toxicity and that the immortalized human lymphocytes model might be an efficient tool for the detection of genetic biomarkers of susceptibility to chemicals.
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.forename: Lihong
authors.initials: L
authors.lastname: Yin
authors.forename: Geyu
authors.initials: G
authors.lastname: Liang
authors.forename: Ran
authors.initials: R
authors.lastname: Liu
authors.forename: Kaihong
authors.initials: K
authors.lastname: Fan
authors.forename: Yuepu
authors.initials: Y
authors.lastname: Pu
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People; D001554:Benzene / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D019800:Phenol / Q000378:metabolism / Q000494:pharmacology; D055815:Young Adult
chemical_list: D019800:Phenol; D019392:Cytochrome P-450 CYP2E1; D001554:Benzene