Valinluck Victoria, Sowers Lawrence C
Department of Biochemistry and Microbiology, School of Medicine, Loma Linda University, Loma Linda, California 92354, USA.
Cancer Res. 2007 Jun 15;67(12):5583-6. doi: 10.1158/0008-5472.CAN-07-0846.
Aberrant methylation patterns have long been known to exist in the promoter regions of key regulatory genes in the DNA of tumor cells. However, the mechanisms by which these methylation patterns become altered during the transformation of normal cells to tumor cells have remained elusive. We have recently shown in in vitro studies that inflammation-mediated halogenated cytosine damage products can mimic 5-methylcytosine in directing enzymatic DNA methylation and in enhancing the binding of methyl-binding proteins whereas certain oxidative damage products inhibit both. We have therefore proposed that cytosine damage products could potentially interfere with normal epigenetic control by altering DNA-protein interactions critical for gene regulation and the heritable transmission of methylation patterns. These inflammation-mediated cytosine damage products may provide, in some cases, a mechanistic link between inflammation and cancer.
长期以来，人们已知肿瘤细胞DNA中关键调控基因的启动子区域存在异常甲基化模式。然而，在正常细胞向肿瘤细胞转化过程中，这些甲基化模式发生改变的机制仍不清楚。我们最近在体外研究中表明，炎症介导的卤代胞嘧啶损伤产物在指导酶促DNA甲基化以及增强甲基结合蛋白的结合方面可以模拟5-甲基胞嘧啶，而某些氧化损伤产物则两者都抑制。因此，我们提出胞嘧啶损伤产物可能通过改变对基因调控和甲基化模式的可遗传传递至关重要的DNA-蛋白质相互作用，潜在地干扰正常的表观遗传控制。在某些情况下，这些炎症介导的胞嘧啶损伤产物可能提供炎症与癌症之间的机制联系。
