Modulation of DNA hypomethylation as a surrogate endpoint biomarker for chemoprevention of colon cancer.
Modulation of DNA hypomethylation as a surrogate endpoint biomarker for chemoprevention of colon cancer.
复制标题
DNA 低甲基化的调节作为结肠癌化学预防的替代终点生物标志物。
DOI：
10.1002/mc.20003
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发表时间：
2004
影响因子：
4.6
通讯作者：
Pereira,MichaelA
中科院分区：
文献类型：
--
作者：
Tao,Lianhui;Wang,Wei;Kramer,PaulaM;Lubet,RonaldA;Steele,VernonE;Pereira,MichaelA
替代终点生物标志物正在开发作为化学预防剂功效的指标。这些生物标志物是分子和生物学终点，可以通过化学预防剂根据其预防癌症的功效进行调节。 DNA 低甲基化是结肠肿瘤中常见的改变，有可能受到化学预防剂的调节，因此可用作替代终点生物标志物。在雄性 F344 大鼠中，评估了对预防结肠癌有效或无效的药物调节氧化偶氮甲烷诱导的结肠肿瘤 DNA 低甲基化的能力。使用小鼠单克隆抗 5-甲基胞嘧啶抗体通过斑点印迹分析测定 DNA 甲基化。与正常结肠粘膜相比，结肠肿瘤的 DNA 甲基化减少了 70%。使用经证明可预防结肠癌的药物（氯化钙、α-二氟甲基鸟氨酸 [DFMO]、吡罗昔康和舒林酸）治疗 7 天后，肿瘤中的 DNA 甲基化增加，而经证明不能预防大鼠结肠癌的药物（低剂量阿司匹林、2-羧基苯基视黄酰胺 [2-CPR]、槲皮素、9-顺视黄酸和芦丁）并未增加 DNA 甲基化甲基化。结果表明，逆转结肠肿瘤中 DNA 低甲基化的能力可作为结肠癌化学预防的替代终点生物标志物。 © 2004 Wiley-Liss, Inc.
Surrogate end‐point biomarkers are being developed as indicators of the efficacy of chemopreventive agents. These biomarkers are molecular and biological end‐points that can be modulated by chemopreventive agents in accordance with their efficacy to prevent cancer. DNA hypomethylation is a common alteration found in colon tumors that has the potential of being modulated by chemopreventive agents and thus being useful as a surrogate end‐point biomarker. Agents that were either effective or ineffective in preventing colon cancer were evaluated for the ability to modulate DNA hypomethylation in azoxymethane‐induced colon tumors in male F344 rats. DNA methylation was determined by Dot Blot Analysis using a mouse monoclonal anti‐5‐methylcytosine antibody. Colon tumors had a 70% reduction in DNA methylation relative to normal colonic mucosa. DNA methylation in the tumors was increased by 7 days of treatment with agents that have been shown to prevent colon cancer (calcium chloride, α‐diflouromethylornithine [DFMO], piroxicam, and sulindac), whereas agents shown not to prevent colon cancer in rats (low dose aspirin, 2‐carboxyphenyl retinamide [2‐CPR], quercetin, 9‐cisretinoic acid, and rutin) did not increase DNA methylation. The results suggest that the ability to reverse the DNA hypomethylation in colon tumors could be useful as a surrogate end‐point biomarker for chemoprevention of colon cancer. © 2004 Wiley‐Liss, Inc.