Sensitivity and dose dependency of radiation-induced injury in hematopoietic stem/progenitor cells in mice

Sci Rep. 2015 Jan 27:5:8055. doi: 10.1038/srep08055.

Abstract

We evaluated the sensitivity and dose dependency of radiation-induced injury in hematopoietic stem/progenitor cells. Adult C57BL/6 mice were daily exposed to 0, 2, 10, 50, and 250 mGy γ-ray for 1 month in succession, respectively. The damage of hematopoietic stem/progenitor cells in bone marrow were investigated within 2 hours (acute phase) or at 3 months (chronic phase) after the last exposure. Daily exposure to over 10 mGy γ-ray significantly decreased the number and colony-forming capacity of hematopoietic stem/progenitor cells at acute phase, and did not completely recover at chronic phase with 250 mGy exposure. Interestingly, the daily exposure to 10 or 50 mGy γ-ray decreased the formation of mixed types of colonies at chronic phase, but the total number of colonies was comparable to control. Immunostaining analysis showed that the formation of 53BP1 foci in c-kit(+) stem/progenitor cells was significantly increased with daily exposure to 50 and 250 mGy at acute phase, and 250 mGy at chronic phase. Many genes involved in toxicity responses were up- or down-regulated with the exposures to all doses. Our data have clearly shown the sensitivity and dose dependency of radiation-induced injury in hematopoietic stem/progenitor cells of mice with daily exposures to 2 ~ 250 mGy γ-ray.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Cells, Cultured
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA-Binding Proteins / metabolism
  • Dose-Response Relationship, Radiation
  • Down-Regulation / radiation effects
  • Flow Cytometry
  • Gamma Rays*
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Proto-Oncogene Proteins c-kit / metabolism
  • Radiation Injuries* / metabolism
  • Radiation Injuries* / pathology
  • Reactive Oxygen Species / metabolism
  • Tumor Suppressor p53-Binding Protein 1
  • Up-Regulation / radiation effects

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Reactive Oxygen Species
  • Trp53bp1 protein, mouse
  • Tumor Suppressor p53-Binding Protein 1
  • Proto-Oncogene Proteins c-kit