Whole body proton irradiation causes acute damage to bone marrow hematopoietic progenitor and stem cells in mice

Int J Radiat Biol. 2017 Dec;93(12):1312-1320. doi: 10.1080/09553002.2017.1356941. Epub 2017 Aug 7.

Abstract

Purpose: Exposure to proton irradiation during missions in deep space can lead to bone marrow injury. The acute effects of proton irradiation on hematopoietic stem and progenitor cells remain undefined and thus were investigated.

Materials and methods: We exposed male C57BL/6 mice to 0.5 and 1.0 Gy proton total body irradiation (proton-TBI, 150 MeV) and examined changes in peripheral blood cells and bone marrow (BM) progenitors and LSK cells 2 weeks after exposure.

Results: 1.0 Gy proton-TBI significantly reduced the numbers of peripheral blood cells compared to 0.5 Gy proton-TBI and unirradiated animals, while the numbers of peripheral blood cell counts were comparable between 0.5 Gy proton-TBI and unirradiated mice. The frequencies and numbers of LSK cells and CMPs in BM of 0.5 and 1.0 Gy irradiated mice were decreased in comparison to those of normal controls. LSK cells and CMPs and their progeny exhibited a radiation-induced impairment in clonogenic function. Exposure to 1.0 Gy increased cellular apoptosis but not the production of reactive oxygen species (ROS) in CMPs two weeks after irradiation. LSK cells from irradiated mice exhibited an increase in ROS production and apoptosis.

Conclusion: Exposure to proton-TBI can induce acute damage to BM progenitors and LSK cells.

Keywords: Proton irradiation; apoptosis; hematopoietic stem cells; reactive oxygen species.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / radiation effects
  • Blood Cell Count
  • Bone Marrow Cells / cytology*
  • Dose-Response Relationship, Radiation
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / radiation effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress / radiation effects
  • Protons / adverse effects*
  • Whole-Body Irradiation / adverse effects*

Substances

  • Protons