Early- and late-occurring damage in bone marrow cells of male CBA/Ca mice exposed whole-body to 1 GeV/n 48Ti ions

Int J Radiat Biol. 2021;97(4):517-528. doi: 10.1080/09553002.2021.1884312. Epub 2021 Mar 8.

Abstract

Purpose: To determine the early- and late-occurring damage in the bone marrow (BM) and peripheral blood cells of male CBA/Ca mice after exposure to 0, 0.1, 0.25, or 0.5 Gy of 1 GeV/n titanium (48Ti) ions (one type of space radiation).

Method: We used the mouse in vivo blood-erythrocyte micronucleus (MN) assay for evaluating the cytogenetic effects of various doses of 1 GeV/n 48Ti ions. The MN assay was coupled with the characterization of epigenetic alterations (the levels of global 5-methylcytosine and 5-hydroxymethylcytosine) in DNA samples isolated from BM cells. These analyses were performed in samples collected at an early time-point (1 week) and a late time-point (6 months) post-irradiation.

Results: Our results showed that 48Ti ions induced genomic instability in exposed mice. Significant dose-dependent loss of global 5-hydroxymethylcytosine was found but there were no changes in global 5-methylcytosine levels.

Conclusion: Since persistent genomic instability and loss of global 5-hydroxymethylcytosine are linked to cancer, our findings suggest that exposure to 48Ti ions may pose health risks.

Keywords: Bone marrow; DNA methylation; early- and late-occurring radiation-induced damage; global 5-hydroxymethylcytosine; global 5-methylcytosine.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / radiation effects*
  • DNA Damage
  • Dose-Response Relationship, Radiation
  • Gamma Rays / adverse effects
  • Male
  • Mice
  • Mice, Inbred CBA
  • Radioisotopes / adverse effects
  • Titanium / adverse effects*
  • Whole-Body Irradiation / adverse effects*

Substances

  • Radioisotopes
  • Titanium