Cho Yoon, Song Mi-Kyung, Ryu Jae-Chun
Korea Institute of Science and Technology, Seoul, Republic of Korea.
Korea Institute of Toxicology, Jeongeup, Republic of Korea.
PeerJ. 2021 Feb 4;9:e10779. doi: 10.7717/peerj.10779. eCollection 2021.
Numerous studies have investigated the relationship of environmental exposure, epigenetic effects, and human diseases. These linkages may contribute to the potential toxicity mechanisms of environmental chemicals. Here, we investigated the epigenetic pulmonary response of hexanal, a major indoor irritant, following inhalation exposure in F-344 rats.
Based on DNA methylation profiling in gene promoter regions, we identified hexanal-characterized methylated sites and target genes using an unpaired t-test with a fold-change cutoff of ≥ 3.0 and a -value < 0.05. We also conducted an integrated analysis of DNA methylation and mRNA expression data to identify core anti-correlated target genes of hexanal exposure. To further investigate the potential key biological processes and pathways of core DNA methylated target genes, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed.
Thirty-six dose-dependent methylated genes and anti-correlated target genes of DNA methylation and mRNA in lung tissue of hexanal exposed F-344 rats were identified. These genes were involved in diverse biological processes such as neuroactive ligand-receptor interaction, protein kinase cascade, and intracellular signaling cascade associated with pulmonary toxicity. These results suggest that novel DNA methylation-based epigenetic biomarkers of exposure to hexanal and elucidate the potential pulmonary toxicological mechanisms of action of hexanal.
众多研究探讨了环境暴露、表观遗传效应与人类疾病之间的关系。这些联系可能有助于揭示环境化学物质的潜在毒性机制。在此，我们研究了F-344大鼠吸入暴露于主要室内刺激物己醛后的表观遗传肺部反应。
基于基因启动子区域的DNA甲基化谱，我们使用不成对t检验，以≥3.0的倍数变化截止值和<0.05的P值，鉴定了己醛特征性甲基化位点和靶基因。我们还对DNA甲基化和mRNA表达数据进行了综合分析，以鉴定己醛暴露的核心反相关靶基因。为了进一步研究核心DNA甲基化靶基因的潜在关键生物学过程和途径，我们进行了基因本体论和京都基因与基因组百科全书途径富集分析。
在暴露于己醛的F-344大鼠肺组织中，鉴定出36个剂量依赖性甲基化基因以及DNA甲基化与mRNA的反相关靶基因。这些基因参与了多种生物学过程，如神经活性配体-受体相互作用、蛋白激酶级联反应以及与肺毒性相关的细胞内信号级联反应。这些结果表明，基于DNA甲基化的新型己醛暴露表观遗传生物标志物得以确定，并阐明了己醛潜在的肺毒理学作用机制。
