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Detection of CYP2E1, a Genetic Biomarker of Susceptibility to Benzene Metabolism Toxicity in Immortal Human Lymphocytes Derived from the Han Chinese Population
  • 时间:0
  • 分类:Q346.5[生物学—遗传学] X524.031[环境科学与工程—环境工程]
  • 作者机构:[1]Key Laboratory of Environmental Medicine Engineering, Ministry of Education,' School of Public Health,Southeast University, Nanjing 210009, Jiangsu, China
  • 相关基金:This work was supported by the National Natural Science Foundation of China (Grant No: 30671731, 30901168) and the Doctoral Program of Higher Education of China (Grant No: 20070286069).
中文摘要:

客观细胞色素 P450 2E1 (CYP2E1 ) 是涉及对苯的氧化压力回答的重要使骨头髓毒性和白血病产生代射变化酶,与联系的化学药品。我们试图在环境、职业的暴露预防的支持识别危险性的 CYP2E1 基因 biomarkers 到苯毒性,并且测试用不朽的人的淋巴细胞的一个模型是否可能是为检测基因 biomarkers 的一个有效工具。使不朽的人的淋巴细胞房间在四个 CYP2E1 SNP 地点上与独立遗传型衬里的方法与 0.01% 酚被导致,苯的代谢物。CYP2E1 基因功能被 mRNA 表示和酶活动评估。DNA 损坏被单个房间的胶化电气泳动(SCGE ) 测量。在四 SNP 之中的结果,有 rs2070673TT 和 rs2030920CC 的房间在一样的 SNP 地点比另外的遗传型显示出 CYP2E1 抄写和酶的活动的高水平。有更高的基因表示遗传型的房间也与更低的基因表示遗传型相比显示出更高的彗星率。这些结果建议那 CYP2E1 rs2070673 和 rs2030920 的结论可能是到苯毒性的危险性的基因 biomarkers,使不朽的人的淋巴细胞当模特儿,这可能是为到化学药品的危险性的基因 biomarkers 的察觉的一个有效工具。

英文摘要:

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 ~YP2E1 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. Conclusion 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.

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