Journal
SCIENTIFIC REPORTS
Volume 8, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41598-018-24755-8
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Funding
- US National Aeronautics and Space Administration NSCOR Program [NNX11AC30G, NNX15AD63G]
- Winship Biostatistics and Bioinformatics Shared Resource
- Emory Integrated Genomics Shared Resource
- NCI Cancer Center Support Grant [1P30-CA0138292]
- NASA [804565, NNX11AC30G, 148762, NNX15AD63G] Funding Source: Federal RePORTER
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Human deep space and planetary travel is limited by uncertainties regarding the health risks associated with exposure to galactic cosmic radiation (GCR), and in particular the high linear energy transfer (LET), heavy ion component. Here we assessed the impact of two high-LET ions Fe-56 and Si-28, and low-LET X rays on genome-wide methylation patterns in human bronchial epithelial cells. We found that all three radiation types induced rapid and stable changes in DNA methylation but at distinct subsets of CpG sites affecting different chromatin compartments. The 56Fe ions induced mostly hypermethylation, and primarily affected sites in open chromatin regions including enhancers, promoters and the edges (shores) of CpG islands. The Si-28 ion-exposure had mixed effects, inducing both hyper and hypomethylation and affecting sites in more repressed heterochromatic environments, whereas X rays induced mostly hypomethylation, primarily at sites in gene bodies and intergenic regions. Significantly, the methylation status of Fe-56 ion sensitive sites, but not those affected by X ray or Si-28 ions, discriminated tumor from normal tissue for human lung adenocarcinomas and squamous cell carcinomas. Thus, high-LET radiation exposure leaves a lasting imprint on the epigenome, and affects sites relevant to human lung cancer. These methylation signatures may prove useful in monitoring the cumulative biological impact and associated cancer risks encountered by astronauts in deep space.
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