Genome-wide study of DNA methylation alterations in response to diazinon exposure in vitro.
Genome-wide study of DNA methylation alterations in response to diazinon exposure in vitro.
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DOI：
10.1016/j.etap.2012.07.012
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发表时间：
2012-11
影响因子：
4.3
通讯作者：
Hou L
中科院分区：
文献类型：
--
作者：
Zhang X;Wallace AD;Du P;Lin S;Baccarelli AA;Jiang H;Jafari N;Zheng Y;Xie H;Soares MB;Kibbe WA;Hou L
农药暴露一再与癌症有关。然而，分子机制在很大程度上是不确定的。在这项研究中，我们研究了暴露于二嗪农（一种与癌症相关的常见有机磷酸盐）是否会诱导DNA甲基化改变。我们使用Illumina Infinium HumanMethylation27 BeadChip对暴露于二嗪农和乙醇的人造血K562细胞的DNA样本进行了全基因组DNA甲基化分析。采用贝叶斯校正t检验鉴定差异甲基化基因启动子CpG位点。我们鉴定出984个基因中的1069个CpG位点在重氮肼处理的细胞中发生了显著的甲基化变化。基因本体分析表明，部分基因为肿瘤抑制基因，如TP53INP1（3.0倍，q值<0.001）、PTEN(2.6倍，q值<0.001)；部分基因位于肿瘤相关通路，如HDAC3(2.2倍，q值=0.002)；部分基因功能未知。我们的研究结果提供了直接的实验证据，表明二嗪农可能改变基因启动子DNA甲基化水平，这可能在癌症发展中发挥病理作用。
Pesticide exposure has repeatedly been associated with cancers. However, molecular mechanisms are largely undetermined. In this study, we examined whether exposure to diazinon, a common organophosphate that has been associated with cancers, could induce DNA methylation alterations. We conducted genome-wide DNA methylation analyses on DNA samples obtained from human hematopoietic K562 cell exposed to diazinon and ethanol using the Illumina Infinium HumanMethylation27 BeadChip. Bayesian-adjusted t-tests were used to identify differentially methylated gene promoter CpG sites. We identified 1069 CpG sites in 984 genes with significant methylation changes in diazinon-treated cells. Gene ontology analysis demonstrated that some genes are tumor suppressor genes, such as TP53INP1 (3.0-fold, q-value<0.001) and PTEN (2.6-fold, q-value<0.001), some genes are in cancer-related pathways, such as HDAC3 (2.2-fold, q-value=0.002), and some remain functionally unknown. Our results provided direct experimental evidence that diazinon may modify gene promoter DNA methylation levels, which may play a pathological role in cancer development.
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影响因子：
3.6
作者：
Baccarelli A;Bollati V
通讯作者：
Bollati V
影响因子：
4.8
作者：
Browne, R. Orie;Ben Moyal-Segal, Liat;Friedman, Alon
通讯作者：
Friedman, Alon
影响因子：
8.3
作者：
Barr, DB;Allen, R;Needham, LL
通讯作者：
Needham, LL
DOI：
10.1016/0165-1218(94)90071-x
发表时间：
1994-06-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
BIANCHI, L;ZANNOLI, A;CHIESARA, E
通讯作者：
CHIESARA, E
影响因子：
64.5
作者：
Ding, H;Schertzer, M;Lansdorp, PM
通讯作者：
Lansdorp, PM