Particulate matter-induced hypomethylation of Alu and LINE1 in normal human bronchial epithelial cells and epidermal keratinocytes

초록

Background: Airborne particulate matter (PM), a complex mixture of organic and inorganic compounds, is a major public health concern due to its adverse health effects. Understanding the biological action of PM is of particular importance in the improvement of public health. Differential methylation of repetitive elements (RE) by PM might have severe consequences for the structural integrity of the genome and on transcriptional activity, thereby affecting human health. This study aimed to evaluate the effect of inhaled and non-inhaled PM (PM2.5, PM10, and PM10-PAH) exposure on DNA methylation. We quantitatively measured the methylation content of Alu and LINE1 in PM-treated normal human bronchial epithelial cells (NHBE) and normal human epidermal keratinocytes (NHEK) by using whole-genome bisulfite sequencing and pyrosequencing. Results: All PMs exposure significantly lowered Alu and LINE1 methylation in both cells than in mock-treated controls. Hypomethylation was more prominent in PM10-PAH exposed-NHBE and PM10 exposed-NHEK. AIu and LINE1 methylation change exhibited different sensitivity according to the subfamily evolutionary ages, with stronger effects on the oldest L1-M and Alu J in NHBE, and oldest L1-M and youngest Alu S in NHEK. Conclusions: These results demonstrate that the differential susceptibility of PM-induced hypomethylation of Alu and LINE1 depends upon RE evolutionary age and PM type.

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