Abstract
Recent studies have investigated the epigenetic effects of environmental exposure to chemicals on human health. The associations of DNA methylation, environmental exposure and human diseases have been widely demonstrated. However, the use of gene methylation patterns as a predictive biomarker for exposure to environmental toxicants is relatively poorly understood. Here, we focused on low-molecular-weight saturated aliphatic aldehydes (LSAAs), which are important environmental risk factors in humans as major indoor air pollutants. Based on DNA methylation profiling in gene promoter regions, we analysed DNA methylation profiles following exposure of A549 cells to seven LSAAs (propanal, butanal, pentanal, hexanal, heptanal, octanal, and nonanal) to identify LSAA-characterized methylated sites and target genes, as well as to investigate whether exposure to LSAAs contributes to inducing of pulmonary toxicity. Additionally, by integrating DNA methylation and mRNA expression profile analyses, we identified core anti-correlated target genes. Gene ontology analysis of these target genes revealed several key biological processes. These findings suggest that alterations in DNA methylation by exposure to LSAAs provide novel epigenetic biomarkers for risk assessments. This DNA methylation-mRNA approach also reveals potential new mechanistic insights into the epigenetic actions of pulmonary toxicity.
Highlights
Among the epigenetic mechanisms, there has been an increase in the number of DNA methylome studies investigating the effects of human health risk factors including environmental chemicals on disease
To investigate the genome-wide promoter DNA methylation expression profiles in A549 cells exposed to aldehydes, we performed a human 2 × 400 k DNA methylation microarray (Agilent Technologies, Santa Clara, CA, USA)
We identified the total DNA methylation expression patterns in A549 cells exposed to the aldehydes (Fig. 1), and examined the overall DNA methylation levels to identify aldehyde-specific epigenetic DNA methylation markers
Summary
There has been an increase in the number of DNA methylome studies investigating the effects of human health risk factors including environmental chemicals on disease. Numerous studies demonstrating the influence of environmental toxicants on DNA methylation have been linked to human health[7] Various environmental toxicants such as air pollutants, toxic chemicals, and radiation that affect epigenetic processes result from the effects of acute or chronic exposure. To investigate the epigenetic DNA methylation biomarkers of aldehydes on the human respiratory system for health risk assessment, we performed DNA methylome analysis. Following DNA methylation profiling, we performed integrated analyses of the methylation and mRNA data in A549 cells exposed to aldehydes to identify correlations Taken together, these findings indicate the potential pulmonary toxic effects of aldehyde exposure. Such DNA methylation biomarkers improve the understanding of the underlying mechanisms of epigenetic regulation associated with aldehyde exposure
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