Galactic Cosmic Radiation Induces Persistent Epigenome Alterations Relevant to Human Lung Cancer.

Autor: Kennedy EM; Graduate Program in Genetics and Molecular Biology, Emory University, Atlanta, GA, 30322, USA.; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30322, USA., Powell DR; Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, 30322, USA., Li Z; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, 30322, USA., Bell JSK; Graduate Program in Genetics and Molecular Biology, Emory University, Atlanta, GA, 30322, USA.; Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, 30322, USA.; Department of Medicine, University of Chicago, Chicago, IL, USA., Barwick BG; Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, 30322, USA., Feng H; Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA., McCrary MR; Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, 30322, USA., Dwivedi B; Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA., Kowalski J; Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA.; Winship Cancer Institute of Emory University, Atlanta, GA, 30322, USA., Dynan WS; Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, 30322, USA.; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, 30322, USA.; Winship Cancer Institute of Emory University, Atlanta, GA, 30322, USA., Conneely KN; Graduate Program in Genetics and Molecular Biology, Emory University, Atlanta, GA, 30322, USA.; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30322, USA.; Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA., Vertino PM; Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, 30322, USA. pvertin@emory.edu.; Winship Cancer Institute of Emory University, Atlanta, GA, 30322, USA. pvertin@emory.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2018 Apr 30; Vol. 8 (1), pp. 6709. Date of Electronic Publication: 2018 Apr 30.
DOI: 10.1038/s41598-018-24755-8
Abstrakt: 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 56 Fe and 28 Si, 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 56 Fe ions induced mostly hypermethylation, and primarily affected sites in open chromatin regions including enhancers, promoters and the edges ("shores") of CpG islands. The 28 Si 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 56 Fe ion sensitive sites, but not those affected by X ray or 28 Si 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.
Databáze: MEDLINE
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