DNA Methylome Analysis of Saturated Aliphatic Aldehydes in Pulmonary Toxicity

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.