Role of DNA methylation in cell cycle arrest induced by Cr (VI) in two cell lines.
Role of DNA methylation in cell cycle arrest induced by Cr (VI) in two cell lines.
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DNA 甲基化在 Cr (VI) 诱导的两种细胞系细胞周期停滞中的作用。
DOI：
10.1371/journal.pone.0071031
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Lou J;Wang Y;Yao C;Jin L;Wang X;Xiao Y;Wu N;Song P;Song Y;Tan Y;Gao M;Liu K;Zhang X
六价铬[Cr(IV)]是一种众所周知的工业废物和环境污染物，被认为是人类致癌物。但其致癌机制尚不清楚，最近的研究表明DNA甲基化可能在Cr(IV)的致癌作用中发挥重要作用。我们研究的目的是研究 Cr(IV) 对细胞周期进程、整体 DNA 甲基化和 p16 基因 DNA 甲基化的影响。将人 B 类淋巴母细胞系和人肺细胞系 A549 暴露于 5–15 µM 重铬酸钾或 1.25–5 µg/cm2 铬酸铅 2–24 小时。 24小时暴露组中，两种化合物均将细胞周期阻滞于G1期，但整体低甲基化发生早于细胞周期阻滞，且低甲基化状态维持超过20小时。 Cr(IV)尤其是重铬酸钾显着上调p16的mRNA表达，并且细胞周期蛋白依赖性激酶（CDK4和CDK6）的mRNA表达显着下调。但蛋白质表达分析显示p16基因变化很小。定性和定量结果均表明p16的DNA甲基化状态保持不变。总的来说，我们的数据表明，整体低甲基化可能是 Cr(IV) 诱导的 G1 期阻滞的原因，但 DNA 甲基化可能与 Cr(IV) 对 p16 基因的上调无关。
Hexavalent chromium [Cr(IV)], a well-known industrial waste product and an environmental pollutant, is recognized as a human carcinogen. But its mechanisms of carcinogenicity remain unclear, and recent studies suggest that DNA methylation may play an important role in the carcinogenesis of Cr(IV). The aim of our study was to investigate the effects of Cr(IV) on cell cycle progress, global DNA methylation, and DNA methylation of p16 gene. A human B lymphoblastoid cell line and a human lung cell line A549 were exposed to 5–15 µM potassium dichromate or 1.25–5 µg/cm2 lead chromate for 2–24 hours. Cell cycle was arrested at G1 phase by both compounds in 24 hours exposure group, but global hypomethylation occurred earlier than cell cycle arrest, and the hypomethylation status maintained for more than 20 hours. The mRNA expression of p16 was significantly up-regulated by Cr(IV), especially by potassium dichromate, and the mRNA expression of cyclin-dependent kinases (CDK4 and CDK6) was significantly down-regulated. But protein expression analysis showed very little change of p16 gene. Both qualitative and quantitative results showed that DNA methylation status of p16 remained unchanged. Collectively, our data suggested that global hypomethylation was possibly responsible for Cr(IV) - induced G1 phase arrest,but DNA methylation might not be related to up-regulation of p16 gene by Cr(IV).
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