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癌症风险中的表观遗传因素：化学致癌物对人 TK6 细胞中全球 DNA 甲基化模式的影响。

Epigenetic factors in cancer risk: effect of chemical carcinogens on global DNA methylation pattern in human TK6 cells.

机构信息

Department of Occupational, Environmental and Insurance Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.

出版信息

PLoS One. 2012;7(4):e34674. doi: 10.1371/journal.pone.0034674. Epub 2012 Apr 11.

DOI:10.1371/journal.pone.0034674
PMID:22509344
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3324488/
Abstract

In the current study, we assessed the global DNA methylation changes in human lymphoblastoid (TK6) cells in vitro in response to 5 direct and 10 indirect-acting genotoxic agents. TK6 cells were exposed to the selected agents for 24 h in the presence and/or absence of S9 metabolic mix. Liquid chromatography-mass spectrometry was used for quantitative profiling of 5-methyl-2'-deoxycytidine. The effect of exposure on 5-methyl-2'-deoxycytidine between control and exposed cultures was assessed by applying the marginal model with correlated residuals on % global DNA methylation data. We reported the induction of global DNA hypomethylation in TK6 cells in response to S9 metabolic mix, under the current experimental settings. Benzene, hydroquinone, styrene, carbon tetrachloride and trichloroethylene induced global DNA hypomethylation in TK6 cells. Furthermore, we showed that dose did not have an effect on global DNA methylation in TK6 cells. In conclusion we report changes in global DNA methylation as an early event in response to agents traditionally considered as genotoxic.

摘要

在本研究中，我们评估了人类淋巴母细胞系（TK6）细胞在体外对 5 种直接作用和 10 种间接作用遗传毒性试剂的全球 DNA 甲基化变化。在存在和/或不存在 S9 代谢混合物的情况下，将 TK6 细胞暴露于选定的试剂中 24 小时。使用液相色谱-质谱法对 5-甲基-2'-脱氧胞苷进行定量分析。通过在 %全基因组 DNA 甲基化数据上应用具有相关残差的边缘模型，评估暴露对对照和暴露培养物之间 5-甲基-2'-脱氧胞苷的影响。在当前的实验条件下，我们报告了 S9 代谢混合物诱导 TK6 细胞的全基因组 DNA 低甲基化。苯、对苯二酚、苯乙烯、四氯化碳和三氯乙烯诱导 TK6 细胞的全基因组 DNA 低甲基化。此外，我们还表明，剂量对 TK6 细胞的全基因组甲基化没有影响。总之，我们报告了作为对传统认为遗传毒性的试剂的早期反应的全基因组 DNA 甲基化变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd5/3324488/37998a9c46ac/pone.0034674.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd5/3324488/28d4b34003e4/pone.0034674.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd5/3324488/94f9c366ed8a/pone.0034674.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd5/3324488/37998a9c46ac/pone.0034674.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd5/3324488/28d4b34003e4/pone.0034674.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd5/3324488/94f9c366ed8a/pone.0034674.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd5/3324488/37998a9c46ac/pone.0034674.g003.jpg

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