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Abstract
Background: Environmental exposure, medical diagnostic and therapeutic applications, and industrial utilization of radionuclides have prompted a growing focus on the risks associated with low-dose radiation (< 100 mGy). Current evidence suggests that such radiation can induce epigenetic changes. Nevertheless, whether exposure to low-dose radiation can disrupt endothelial cell function at the molecular level is unclear. Because endothelial cells play crucial roles in cardiovascular health and disease, we aimed to investigate whether low-dose radiation could lead to differential DNA methylation patterns at the genomic level in endothelial cell (EC) lines.

Methods: We screened for changes in DNA methylation patterns in primary human aortic (HAECs) and coronary artery endothelial cells following exposure to low-dose ionizing radiation. Using a subset of genes altered via DNA methylation by low-dose irradiation, we performed gene ontology (GO) analysis to predict the possible biological network mediating the effect of low-dose radiation. In addition, we performed comprehensive validation using methylation and gene expression analyses, and ChIP assay to identify useful biomarkers among candidate genes for use in detecting low-dose radiation exposure in human primary normal ECs.

Results: Low-dose radiation is sufficient to induce global DNA methylation alterations in normal EC lines. GO analysis demonstrated that these hyper- or hypo-methylated genes were linked to diverse biological pathways. Our findings indicated a robust correlation between promoter hypermethylation and transcriptional downregulation of four genes (PGRMC1, UNC119B, RERE, and FNDC3B) in response to low-dose ionizing radiation in HAECs.

Conclusions: Based on these findings, the identified genes can serve as potential DNA methylation biomarkers for the assessment of cardiovascular risk upon exposure to low-dose radiation.

Affiliations

Jihye Park # 1, Hae-June Lee # 2, Yu Kyeong Han 3, Keunsoo Kang 1, Joo Mi Yi 4
1Department of Microbiology, Dankook University, Cheonan, 31116, South Korea.
2Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul, 01812, South Korea.
3Department of Microbiology and Immunology, College of Medicine, Inje University, Busan, 47392, South Korea.
4Department of Microbiology and Immunology, College of Medicine, Inje University, Busan, 47392, South Korea. jmyi76@inje.ac.kr.
#Contributed equally.