Dataset Information

DNA methylome signatures as epigenetic biomarkers of hexanal associated with lung toxicity.

ABSTRACT:

Background

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.

Methods

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 p-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.

Results

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.

SUBMITTER: Cho Y

PROVIDER: S-EPMC7868067 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

DNA methylome signatures as epigenetic biomarkers of hexanal associated with lung toxicity.

Cho Yoon Y Song Mi-Kyung MK Ryu Jae-Chun JC

PeerJ 20210204

<h4>Background</h4>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.<h4>Methods</h4>Based on DNA methylation profiling in gene promoter regions, we identified hexanal-characterized methylated sites ...[more]

PMID: 33604181

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Project description:Reproductive factors have been linked to both breast cancer and DNA methylation, suggesting methylation as an important mechanism by which reproductive factors impact on disease risk. However, few studies have investigated the link between reproductive factors and DNA methylation in humans. Genome-wide methylation in peripheral blood lymphocytes of 376 healthy women from the prospective EPIC study was investigated using LUminometric Methylation Assay (LUMA). Also, methylation of 458877 CpG sites was additionally investigated in an independent group of 332 participants of the EPIC-Italy sub-cohort, using the Infinium HumanMethylation 450 BeadChip. Multivariate logistic regression and linear models were used to investigate the association between reproductive risk factors and genome wide and CpG-specific DNA methylation, respectively. Menarcheal age was inversely associated with global DNA methylation as measured with LUMA. For each yearly increase in age at menarche, the risk of having genome wide methylation below median level was increased by 32% (OR:1.32, 95%CI:1.14-1.53). When age at menarche was treated as a categorical variable, there was an inverse dose-response relationship with LUMA methylation levels (OR(12-14 vs. ?11 yrs):1.78, 95%CI:1.01-3.17 and OR(?15 vs. ?11 yrs):4.59, 95%CI:2.04-10.33; P for trend<0.0001). However, average levels of global methylation as measured by the Illumina technology were not significantly associated with menarcheal age. In locus by locus comparative analyses, only one CpG site had significantly different methylation depending on the menarcheal age category examined, but this finding was not replicated by pyrosequencing in an independent data set. This study suggests a link between age at menarche and genome wide DNA methylation, and the difference in results between the two arrays suggests that repetitive element methylation has a role in the association. Epigenetic changes may be modulated by menarcheal age, or the association may be a mirror of other important changes in early life that have a detectable effect on both methylation levels and menarcheal age.

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Dataset Information

DNA methylome signatures as epigenetic biomarkers of hexanal associated with lung toxicity.

Background

Methods

Results

Publications

DNA methylome signatures as epigenetic biomarkers of hexanal associated with lung toxicity.

Similar Datasets

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