Long-term epigenetic effects of exposure to low doses of 56Fe in the mouse lung

Etienne Nzabarushimana, Isabelle R. Miousse, Lijian Shao, Jianhui Chang, Antiño R. Allen, Jennifer Turner, Blair Stewart, Jacob Raber, Igor Koturbash

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18 Scopus citations

Abstract

Despite significant progress, the long-term health effects of exposure to high charge (Z) and energy (E) nuclei (HZEs) and the underlying mechanisms remain poorly understood. Mouse studies show that space missions can result in pulmonary pathological states. The goal of this study was to evaluate the pro-fibrotic and pro-carcinogenic effects of exposure to low doses of heavy iron ions (56Fe) in the mouse lung. Exposure to 56Fe (600 MeV; 0.1, 0.2 and 0.4 Gy) resulted in minor pro-fibrotic changes, detected at the beginning of the fibrotic phase (22 weeks post exposure), which were exhibited as increased expression of chemokine Ccl3, and interleukin Il4. Epigenetic alterations were exhibited as global DNA hypermethylation, observed after exposure to 0.4 Gy. Cadm1, Cdh13, Cdkn1c, Mthfr and Sfrp1 were significantly hypermethylated after exposure to 0.1 Gy, while exposure to higher doses resulted in hypermethylation of Cdkn1c only. However, expression of these genes was not affected by any dose. Congruently with the observed patterns of global DNA methylation, DNA repetitive elements were hypermethylated after exposure to 0.4 Gy, with minor changes observed after exposure to lower doses. Importantly, hypermethylation of repetitive elements coincided with their transcriptional repression. The findings of this study will aid in understanding molecular determinants of pathological states associated with exposure to 56Fe, as well as serve as robust biomarkers for the delayed effects of irradiation. Further studies are clearly needed to investigate the persistence and outcomes of molecular alterations long term after exposure.

Original languageEnglish (US)
Pages (from-to)823-828
Number of pages6
JournalJournal of radiation research
Volume55
Issue number4
DOIs
StatePublished - Jul 2014

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Keywords

  • DNA methylation
  • epigenetics
  • heavy iron ions
  • lung cancer
  • pulmonary fibrosis
  • repetitive elements

ASJC Scopus subject areas

  • Radiation
  • Radiology Nuclear Medicine and imaging
  • Health, Toxicology and Mutagenesis

Cite this

Nzabarushimana, E., Miousse, I. R., Shao, L., Chang, J., Allen, A. R., Turner, J., Stewart, B., Raber, J., & Koturbash, I. (2014). Long-term epigenetic effects of exposure to low doses of 56Fe in the mouse lung. Journal of radiation research, 55(4), 823-828. https://doi.org/10.1093/jrr/rru010