Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu, China.
Biomed Environ Sci. 2011 Jun;24(3):300-9. doi: 10.3967/0895-3988.2011.03.014.
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.
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).
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.
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.
细胞色素 P450 2E1（CYP2E1）是一种重要的代谢酶，参与苯的氧化应激反应，苯是一种与骨髓毒性和白血病有关的化学物质。我们旨在确定 CYP2E1 遗传生物标志物对苯毒性的易感性，以支持环境和职业暴露的预防，并测试使用永生化人淋巴细胞的模型是否可能是检测遗传生物标志物的有效工具。
用 0.01%苯酚诱导具有四个 CYP2E1 SNP 位点独立基因型的永生化人淋巴细胞系，苯酚是苯的代谢物。通过 mRNA 表达和酶活性评估 CYP2E1 基因功能。通过单细胞凝胶电泳（SCGE）测量 DNA 损伤。
在四个 SNP 中，rs2070673TT 和 rs2030920CC 基因型的细胞比同一 SNP 位点的其他基因型具有更高的 CYP2E1 转录和酶活性水平。具有更高基因表达基因型的细胞也表现出比具有较低基因表达基因型更高的彗星率。
这些结果表明，CYP2E1 rs2070673 和 rs2030920 可能是苯毒性易感性的遗传生物标志物，并且永生化人淋巴细胞模型可能是检测化学物质易感性遗传生物标志物的有效工具。
