苯可造成血液损伤，其作用机制尤其是致白血病等血液肿瘤机制不清。DNA损伤修复可能在肿瘤发生中起重要作用。本项目以临床儿童白血病患者为观察对象，分析解旋酶WRN、XPD基因甲基化状态、基因表达，进行异常甲基化位点功能分析，了解叶酸含量水平；利用苯代谢物氢醌染毒正常小鼠骨髓细胞、白血病细胞株，观察去甲基化药物对WRN、XPD基因异常甲基化状态、基因表达的影响，结合干扰RNA技术进一步研究WRN、XPD基因在苯致血液损伤中经ATM/ATR信号转导通路对细胞增殖的影响；利用动物实验，观察叶酸对苯致WRN、XPD基因异常甲基化、基因表达改变的干预效果。本研究利用人群研究、体外细胞培养、实验动物等三个实验体系，从DNA损伤修复角度阐释解旋酶WRN、XPD基因在苯致血液损伤中的分子作用机制，为寻找监测苯致血液损伤发生发展的早期生物学标志提供线索，为苯致血液损伤的防治提出新的思路和方向。

Benzene can cause blood injury. Its mechanism of injury is not clear in particular pathogenesis of leukemia and other blood cancer. Repair of DNA damage may play an important role in the tumorigenesis. This project uses clinical leukemia children as the observation object, to observe the effect of the helicase WRN, XPD gene methylation status on gene expression, to conduct the analysis of anomalousb methylation, and to get the folic acid levels of the patients. Uses the benzene metabolites in normal mouse bone marrow cells and leukemia cell lines, to observe the WRN, XPD gene methylation status and the effect of gene expression before and after using of demethylation drug, and at the same time, combining with interference RNA, study how WRN and XPD gene, in benzene induced damage in blood, affect on cell proliferation through ATM/ATR signal transduction pathway. Through animal experiments, observes the folic acid's intervening effect on benzene induced WRN, XPD anomalous gene methylation and the change of gene expression. This study will use three experimental systems: population-based study, vitro cell culturing and animal experiment, from the perspective of repair of DNA damage, explain the molecular mechanism of helicase WRN and XPD gene changes in benezene induced blood injury, trying to provide clues for searching the early biological signs of monitoring benzene induced blood injury, and trying to give new ideas in prevention and controlling of blood damage induced by benzene.