Long-term effects of combined exposures to simulated microgravity and galactic cosmic radiation on the mouse lung: sex-specific epigenetic reprogramming.
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| Title: | Long-term effects of combined exposures to simulated microgravity and galactic cosmic radiation on the mouse lung: sex-specific epigenetic reprogramming. |
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| Authors: | Clement, Kirsten1 (AUTHOR), Nemec-Bakk, Ashley S.2 (AUTHOR), Jun, Se-Ran3 (AUTHOR), Sridharan, Vijayalakshmi2 (AUTHOR), Patel, Chirayu M.4 (AUTHOR), Williams, D. Keith5 (AUTHOR), Newhauser, Wayne D.6 (AUTHOR), Willey, Jeffrey S.4 (AUTHOR), Williams, Jacqueline7 (AUTHOR), Boerma, Marjan2 (AUTHOR), Chancellor, Jeffrey C.8 (AUTHOR), Koturbash, Igor1 (AUTHOR) ikoturbash@uams.edu |
| Source: | Radiation & Environmental Biophysics. Mar2025, Vol. 64 Issue 1, p17-27. 11p. |
| Subject Terms: | *Galactic cosmic rays, *Life sciences, *Cosmic rays, *DNA methyltransferases, *Ionizing radiation, *Reduced gravity environments |
| Abstract: | Most studies on the effects of galactic cosmic rays (GCR) have relied on terrestrial irradiation using spatially homogeneous dose distributions of mono-energetic beams comprised of one ion species. Here, we exposed mice to novel beams that more closely mimic GCR, namely, comprising poly-energetic ions of multiple species. Six-month-old male and female C57BL/6J mice were exposed to 0 Gy, 0.5 Gy, or 1.5 Gy simplified simulated 5 ion GCR (GCRsim). Exposure to microgravity was simulated using hindlimb unloading (HLU). At nine months post exposure, the mice were terminated to assess for the presence of exposure-induced epigenetic alterations. DNA hypermethylation in the 5'-untranslated regions of Lx_III, MdFanc_I, and MdMus_II families of the Long Interspersed Nucleotide Element 1 (LINE-1) was observed in the lungs of male mice. These effects were accompanied by increases in the expression of DNA methyltransferases Dnmt1 and Dnmt3a, and methyl-binding protein, MecP2. Trends towards DNA hypomethylation, although insignificant, were observed in the lungs of female mice in the HLU + 1.5 Gy GCRsim group. Altogether, our findings suggest persistent and sex-specific epigenetic reprogramming in the mouse lung and suggests that the DNA methylation status of LINE-1 can serve as a robust and reliable biomarker of previous radiation exposure. [ABSTRACT FROM AUTHOR] |
| Database: | Energy & Power Source |
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| Abstract: | Most studies on the effects of galactic cosmic rays (GCR) have relied on terrestrial irradiation using spatially homogeneous dose distributions of mono-energetic beams comprised of one ion species. Here, we exposed mice to novel beams that more closely mimic GCR, namely, comprising poly-energetic ions of multiple species. Six-month-old male and female C57BL/6J mice were exposed to 0 Gy, 0.5 Gy, or 1.5 Gy simplified simulated 5 ion GCR (GCRsim). Exposure to microgravity was simulated using hindlimb unloading (HLU). At nine months post exposure, the mice were terminated to assess for the presence of exposure-induced epigenetic alterations. DNA hypermethylation in the 5'-untranslated regions of Lx_III, MdFanc_I, and MdMus_II families of the Long Interspersed Nucleotide Element 1 (LINE-1) was observed in the lungs of male mice. These effects were accompanied by increases in the expression of DNA methyltransferases Dnmt1 and Dnmt3a, and methyl-binding protein, MecP2. Trends towards DNA hypomethylation, although insignificant, were observed in the lungs of female mice in the HLU + 1.5 Gy GCRsim group. Altogether, our findings suggest persistent and sex-specific epigenetic reprogramming in the mouse lung and suggests that the DNA methylation status of LINE-1 can serve as a robust and reliable biomarker of previous radiation exposure. [ABSTRACT FROM AUTHOR] |
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| ISSN: | 0301634X |
| DOI: | 10.1007/s00411-025-01108-4 |
