中文摘要：

目的探讨叶酸干预对健康人外周血单个核细胞中肿瘤相关基因启动子甲基化状态的影响。方法健康志愿者10人，均分为2组，分别口服叶酸5mg或安慰剂，每日1次，连续3个月。于干预前后，以化学发光酶免疫分析试剂盒测定血清叶酸浓度，亚硫酸氢钠测序PCR（BSP）技术分别检测癌基因c—myc、C—Ha-ras，抑癌基因E—cadherin、p16INK4A和错配修复基因hMLH1的启动子甲基化状态。结果叶酸干预后，干预组血清叶酸水平显著升高（t=-4．739，P％0．05），而对照组无明显变化。叶酸干预3个月后，癌基因c—myc启动子甲基化率分别从干预前的4％、服用1周时的3．3％、服用1个月时的4．1％增加到8％（t=-4．079，P％0．05），而服用安慰剂者无明显变化。叶酸干预前后，其他肿瘤相关基因包括c—Ha-ras、E-cadherin、p16INK4A和hMLH1的启动子甲基化水平无明显改变。结论叶酸干预可升高癌基因c—myc启动子甲基化水平，但不影响抑癌基因E—eadherin、p16INK4A和hMLH1的甲基化状态。

英文摘要：

Objective To investigate the effect of folie acid on the DNA methylation of tumorrelated genes promoters in healthy human peripheral blood mononuclear cells（PBMC）. Methods Ten healthy volunteers were divided into two groups, and were randomized to receive either 5 mg folic acid （n=5）or placebo（n= 5）, one time per day for 3 months. The serum folic acid concentration was detected with chemiluminescence enzyme immunoassay kit before and after the intervention. The methylation statuses of five tumor-related genes promoter, including oncogenes c-myc, c-Ha-ras, tumor suppressor genes p16INK4A, E-cadherin and mismatch repair gene hMLH1 in PBMC were detected by bisufite sequencing. Results After folic acid intervention, the level of serum folic acid increased significantly in intervention group （t=-4. 739, P〈0.05）, however no significant difference in control group. After three-month folic acid intervention, the level of methylation of oncogene c-myc promoter increased from 4%, 3. 3%, 4. 1% before intervention, one week after intervention, one month after intervention respectively to 8 % （t =- 4. 079, P〈0.05）, while no significant change in placebo taken group. Before and after the folic acid intervention, there was no significant difference of DNA methylation of other tumor-related genes promoter, including c-Ha-ras, E-cadherin, p16INK4A and hMLH1. Conclusion Folic acid intervention can up-regulate DNA methylation of oncogene c-myc promoter, but can not affect the promoter methylation status of tumor suppressor genes E-cadherin, p16INK4A and hMLH1.