Response of human hematopoietic stem and progenitor cells to energetic carbon ions

Abstract

Purpose: To characterise the radiation response of human hematopoietic stem and progenitor cells (HSPC) with respect to X and carbon ion irradiation.

Materials and methods: HSPC from peripheral blood of healthy donors treated with granulocyte-colony stimulating factor (G-CSF) were enriched for the transmembrane glycoprotein CD34 (cluster of differentiation) and irradiated with X rays or carbon ions (29 keV/μm monoenergetic beam and 60-85 keV/μm spread-out Bragg peak), mimicking radiotherapy conditions. Apoptotic cell death, cell cycle progression and the frequency of chromosomal aberrations were determined.

Results: After radiation exposure no inhibition in the progression of the cell cycle was detected. However, an enhanced frequency of apoptotic cells and an increase in aberrant cells were observed, both effects being more pronounced for carbon ions than X rays, resulting in a relative biological effectiveness (RBE) of 1.4–1.7. The fraction of complex-type aberrations was higher following carbon ion exposure.

Conclusions: RBE values of carbon ions are low, as expected for radiosensitive cells. The observed frequencies of apoptotic cells and chromosome aberrations in HSPC are similar to those reported for human peripheral blood lymphocytes suggesting that at least with respect to apoptosis and chromosomal aberrations mature lymphocytes reflect the respective radiation responses of their proliferating progenitors.

Keywords:

• hematopoietic stem and progenitor cells
• carbon ions
• RBE
• apoptosis
• cell cycle progression
• chromosomal aberrations

Acknowledgments

This work was supported by GSI, research assignment no. 178 and partly by BMBF, Bonn (Grant No. 02 S 8497). The authors would like to thank the dosimetry and irradiation team for excellent support during accelerator experiments.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.