Impact of proton therapy on the DNA damage induction and repair in hematopoietic stem and progenitor cells

Proton therapy is of great interest to pediatric cancer patients because of its optimal depth dose distribution. In view of healthy tissue damage and the increased risk of secondary cancers, we investigated DNA damage induction and repair of radiosensitive hematopoietic stem and progenitor cells (HSPCs) exposed to therapeutic proton and photon irradiation due to their role in radiation-induced leukemia. Human CD34+ HSPCs were exposed to 6 MV X-rays, mid- and distal spread-out Bragg peak (SOBP) protons at doses ranging from 0.5 to 2 Gy. Persistent chromosomal damage was assessed with the micronucleus assay, while DNA damage induction and repair were analyzed with the gamma-H2AX foci assay. No differences were found in induction and disappearance of gamma-H2AX foci between 6 MV X-rays, mid- and distal SOBP protons at 1 Gy. A significantly higher number of micronuclei was found for distal SOBP protons compared to 6 MV X-rays and mid- SOBP protons at 0.5 and 1 Gy, while no significant differences in micronuclei were found at 2 Gy. In HSPCs, mid-SOBP protons are as damaging as conventional X-rays. Distal SOBP protons showed a higher number of micronuclei in HSPCs depending on the radiation dose, indicating possible changes of the in vivo biological response.

Automated summary

Proton therapy and photon irradiation were investigated for their effects on DNA damage and repair in hematopoietic stem and progenitor cells (HSPCs). The study found that there were no significant differences in the induction and repair of DNA damage between proton therapy and X-ray irradiation. However, proton irradiation caused more severe chromosomal damage in HSPCs compared to X-rays, indicating possible changes in biological response.