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首页> 外文期刊>Oncogene >Early-stage formation of an epigenetic field defect in a mouse colitis model, and non-essential roles of T- and B-cells in DNA methylation induction
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Early-stage formation of an epigenetic field defect in a mouse colitis model, and non-essential roles of T- and B-cells in DNA methylation induction

机译：在小鼠结肠炎模型中的表观遗传田间缺陷的早期形成，以及DNA甲基化诱导中的T-和B细胞的非必要作用

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Epigenetic fields for cancerization are involved in development of human cancers, especially those associated with inflammation and multiple occurrences. However, it is still unclear when such field defects are formed and what component of inflammation is involved in induction of aberrant DNA methylation. Here, in a mouse colitis model induced by dextran sulfate sodium (DSS), we identified three CpG islands specifically methylated in colonic epithelial cells exposed to colitis. Their methylation levels started to increase as early as 8 weeks after DSS treatment and continued to increase until colon cancers developed at 15 weeks. In contrast to the temporal profile of DNA methylation levels, infiltration of inflammatory cells spiked immediately after the DSS treatment and then gradually decreased. Exposure of cultured colonic epithelial cells to DSS did not induce DNA methylation and it was indicated that inflammation triggered by the DSS treatment was responsible for methylation induction. To clarify components of inflammation involved, severe combined immunodeficiency (SCID) mice that lack functional T- and B-cells were similarly treated. Even in SCID mice, DNA methylation, along with colon tumors, were induced at the same levels as in their background strain of mice (C.B17). Comparative analysis of inflammation-related genes showed that Ifng , Il1b and Nos2 had expression concordant with methylation induction whereas Il2 , Il6 , Il10 , Tnf did not. These results showed that an epigenetic field defect is formed at early stages of colitis-associated carcinogenesis and that functional T and B cells are non-essential for the formation.
机译：癌症的表观遗传领域涉及人类癌症的发展，尤其是与炎症和多次出现相关的癌症。然而，当形成这种场缺陷时仍然尚不清楚，并且炎症的组分参与诱导异常DNA甲基化。这里，在由葡聚糖硫酸钠钠（DSS）诱导的小鼠结肠炎模型中，我们鉴定了三种特异性甲基岛，在暴露于结肠炎的结肠上皮细胞中。在DSS治疗后8周开始，它们的甲基化水平开始增加，并继续增加，直至结肠癌在15周内发展。与DNA甲基化水平的时间轮廓相反，在DSS处理后立即掺入炎性细胞的浸润，然后逐渐降低。将培养的结肠上皮细胞暴露于DSS没有诱导DNA甲基化，结果表明DSS处理引发的炎症是甲基化诱导的原因。为了阐明所涉及的炎症的组分，同样处理缺乏功能性T-和B细胞的严重组合免疫缺陷（SCID）小鼠。即使在SCID小鼠中，DNA甲基化以及结肠肿瘤也与小鼠的背景菌株相同的水平诱导（C.B17）。与炎症相关基因的比较分析表明， IFNG， IL1B和 NOS2对甲基化诱导表达式表示，而IL2， IL6， IL10， TNF不是。这些结果表明，在结肠炎相关致癌的早期阶段形成表观遗传域缺陷，并且功能性T和B细胞对形成是非必需的。

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