中文摘要：

目的探讨二甲基肼（DMH）诱导小鼠大肠癌模型中5-脱氧杂氮胞苷（5-aza—dC）预防肿瘤发生的作用机制。方法80只ICR小鼠分为4组，每组20只。包括空白对照组、5-aza—dC对照组、DMH诱癌组和5-aza-dC干预组。处理20周后观察其对肿瘤发生率的影响。实时定量PCR检测Dnmt1、Dnmt3a、Dnmt3b基因和抑癌基因p27^Kip1的表达。结果通过5-aza-dC干预能使诱导的大肠肿瘤发生率从95％降至35％，肿瘤数目（个）由9．43±4．21减少到3．98±2．95，肿瘤最大直径（单位：mm）由6．43±5．12缩小到3．44±2．11，差异有统计学意义（P〈0．05）。实时定量PCR检测发现肿瘤组织中存在Dnmt1和Dnmt3b的高表达，而p27^Kip1的表达量降低。5-aza—dC可以通过抑制甲基化酶活性，防止p27^Kip1基因的高甲基化失活。结论5-aza-dC可以显著降低DMH诱发小鼠大肠癌的发生率，阻止抑癌基因的高甲基化失活可能是5-aza-dC预防肿瘤的重要机制。

英文摘要：

Objective To explore the effect of DNA methyltransferase inhibitor 5-aza-2＇-deoxycy- tidine （5-aza-dC） in preventing colorectal cancer in mice induced by dimethylhydrazine （DMH）. Methods The colorectal neoplasms were induced with DMH in ICR mice and the different doses of 5-aza-dC were administered, then the prevention of colorectal neoplasm by 5-aza-dC was examined. The transcription levels of Dnmts and p27^kipl genes were determined by real-time PCR. Results The treatment of 5-aza-dC reduced the incident of colorectal cancer from 95 % （19/20） to 35% （7/20）, the average tumor amount from 9.43±4.21 to 3.98±2. 95, and the biggest tumor diameter（ram） from 6. 43 ± 5. 12 to 3.44±2. 11 （5-aza-dC group vs the control respectively, P 〈 0.05 ）. Up-regulation of Dnmt1 and Dnmt3b expression and down-regulation of p27^Kip1 expression were detected in the tumor tissues. 5-Aza-dC can reactivate the tumor suppressor genes p27^Kip1 by blocking DNA methylation. Conclusion 5-aza-dC could prevent colorectal neo- plasms in mice induced by DMH. The utilization of epigenetic targets is emerging as an effective and valuable approach to chemotherapy as well as chemoprevention of neoplasms.