DNA methylation in lung tissues of mouse offspring exposed in utero to polycyclic aromatic hydrocarbons.
DNA methylation in lung tissues of mouse offspring exposed in utero to polycyclic aromatic hydrocarbons.
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DOI：
10.1016/j.fct.2017.04.047
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
Benninghoff AD
中科院分区：
文献类型：
--
作者：
Fish TJ;Benninghoff AD
多环芳烃 (PAH) 是一类重要的环境污染物，已知会导致动物肺癌，并被怀疑是人类肺癌致癌物。此外，基于细胞的研究证据表明多环芳烃是表观基因组的调节剂。这项工作的目的是评估子宫内经胎盘 PAH 致癌物二苯并[def,p]屈 (DBC) 或苯并[a]芘 (BaP) 引发的成年后代肺组织中全基因组 DNA 甲基化的模式。使用甲基化 DNA 免疫沉淀 (MeDIP) 和 NimbleGen 小鼠 DNA 甲基化 CpG 岛阵列测定从成年后代获得的正常（未暴露）、正常邻近组织和肺肿瘤组织的全基因组甲基化模式。 45 周龄小鼠接受 BaP 治疗后，肺部肿瘤发生率为 32%，远低于暴露于 DBC 的后代 96%。此外，与女性相比，男性后代似乎更容易受到 BaP 的影响。通过主成分、层次聚类和基因本体分析确定，不同的 DNA 甲基化模式与未暴露的、正常邻近的肺组织和腺癌肺组织相关。从这些甲基化谱中，确定了一组感兴趣的基因，其中包括暴露于环境多环芳烃的动物肺部肿瘤发生过程中表观遗传修饰的潜在重要靶标。
Polycyclic aromatic hydrocarbons (PAHs) comprise an important class of environmental pollutants that are known to cause lung cancer in animals and are suspected lung carcinogens in humans. Moreover, evidence from cell-based studies points to PAHs as modulators of the epigenome. The objective of this work was to assess patterns of genome-wide DNA methylation in lung tissues of adult offspring initiated in utero with the transplacental PAH carcinogens dibenzo[def,p]chrysene (DBC) or benzo[a]pyrene (BaP). Genome-wide methylation patterns for normal (not exposed), normal adjacent and lung tumor tissues obtained from adult offspring were determined using methylated DNA immunoprecipitation (MeDIP) with the NimbleGen mouse DNA methylation CpG island array. Lung tumor incidence in 45-week old mice initiated with BaP was 32%, much lower than that of the DBC-exposed offspring at 96%. Also, male offspring appeared more susceptible to BaP as compared to females. Distinct patterns of DNA methylation were associated with non-exposed, normal adjacent and adenocarcinoma lung tissues, as determined by principal components, hierarchical clustering and gene ontology analyses. From these methylation profiles, a set of genes of interest was identified that includes potential important targets for epigenetic modification during the process of lung tumorigenesis in animals exposed to environmental PAHs.
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