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Effect of simulated galactic cosmic radiation on mouse lung gene expression

ABSTRACT: C57LBL/6 mice (age 24 weeks) were exposed to 0,75 Gy of Si ions, 5-ion simplified GCR simulation, or reference gamma rays. Some mice received nicotinamide riboside countermeasure. Lung tissue was collected after 30 days and flash frozen.

ORGANISM(S): Mus musculus

PROVIDER: GSE199680 | GEO | 2025/03/29

REPOSITORIES: GEO

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Project description: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 56Fe and 28Si, 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 edges (“shores”) of CpG islands. The 28Si 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 56Fe ion irradiation sensitive sites, but not those affected by X ray or 28Si ions, could discriminate 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. The 56Fe ion signature may prove useful in monitoring the cumulative biological impact and associated cancer risks encountered by astronauts in deep space. Genome wide DNA methylation profiling of normal human bronchial epithelial cells irradiated with varying doses of 28Si-ion radiation ( 300 MeV/u at 0, 0.3, 1.0 Gy) , 56Fe-ion radiation (600 MeV/u at 0, 0.1, 0.3, 1.0 Gy) or X rays (320 kV at 0, 1.0 Gy). Triplicate control and irradiated samples were incubated and sampled at 4 timepoints between 2 and 62 days. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across >485,000 CpGs from collected samples. Samples include: 56Fe ions, 4 doses x 4 time points x 3 replicates (4 removed in QC) = 44 samples; 28Si ions = 3 doses x 4 time points x 3 replicates = 36 samples; X ray, 2 doses x 4 time points x 3 replicates (2 removed in QC)= 22 samples.

Project description:Cellular senescence is a protective stress-response that halts cell proliferation to prevent the accumulation of damage. Life on Earth evolved in the presence of constant, low-dose, unavoidable genotoxic stress caused by highly penetrating muons generated by cosmic rays. However, how cosmic background radiation (CBR) shapes senescence remains unclear. We exploited the Canfranc Deep Underground Laboratory (LSC-DUL), which is located 850 meters beneath the Spanish Pyrenees, to compare senescence phenomena in near-surface versus muon-depleted deep underground environments. The LSC-DUL provides 2,450 meters of water-equivalent shielding, reducing the flux of cosmic-ray muons by five orders of magnitude. Human cancer and noncancer cells were subjected to replicative, mitotic, and oxidative insults with diverse DNA damage response (DDR) activation potencies. Muon deprivation modestly but significantly reduced progression to late, lysosome-dependent SA--gal-positive states after low-DDR replicative stressors. However, high-DDR regimens were largely insensitive to the environment. Transcriptomic signatures of senescent states and the qualitative composition of senescence-associated secretory phenotypes (SASPs) were broadly conserved. Conceptually, stressed cells enter a shallow transcriptional and SASP-positive senescent basin that is permissive across CBR conditions. However, they cross a “CBR barrier” into a deeper SA--gal+ attractor less efficiently when ambient radiogenic noise is depleted and DDR amplitude is low. The robust inertia of high DDR damage readily overrides this barrier, ensuring the immediate occupation of the SA--gal+ fate regardless of the muonic environment. Our findings identify cosmogenic muons as evolutionary radiobiological calibrators of senescence decision-making in the near-surface biosphere. They also generate testable predictions for senescence operability in habitats lacking Earth’s characteristic muon flux, such as the Moon and Mars.

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Effect of simulated galactic cosmic radiation on mouse lung gene expression

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