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. 2023 Oct 9;13(1):16995.
doi: 10.1038/s41598-023-42362-0.

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

Simon Sioen  1 , Oniecha Vanhove  2 , Barbara Vanderstraeten  3   4 , Carlos De Wagter  3   4 , Monique Engelbrecht  5 , Charlot Vandevoorde  5   6 , Evan De Kock  5 , Marc-Jan Van Goethem  7 , Anne Vral  2 , Ans Baeyens  2   8
Affiliations

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

Simon Sioen et al. Sci Rep. .

Abstract

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 γ-H2AX foci assay. No differences were found in induction and disappearance of γ-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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
(a) Image of mono and bi-nucleated (BN) CD34+ HPSCs at 400 × magnification. The grey arrow indicates a micronucleus. (b) The graph represents the number of radiation-induced micronuclei (MN) per dose (Gy) scored in 1000 binucleated (BN) CD34+ HSPCs, irradiated with 6 MV X-rays, mid- spread-out Bragg peak (SOBP) protons or distal-SOBP protons, 70 h post-irradiation. The number of donors per condition is shown. Error bars represent the standard deviation of the mean of the donors. Significance is indicated (*p < 0.05).
Figure 2
Figure 2
Image of the γ-H2AX foci present on a sham-irradiated (top) and an irradiated (bottom) CD34+ HSPCs: (a) 4',6-diamidino-2-fenylindool (DAPI) staining (b) γ-H2AX foci on the fluorescein isothiocyanate (FITC) channel c. Merged picture. Graph shows the mean radiation-induced γ-H2AX foci in CD34+ HSPCs at 30 min, 2 h and 24 h post-irradiation exposure to 6 MV X-rays, mid- spread-out Bragg peak (SOBP) and distal SOBP protons. Error bars represent the standard deviation of the mean over the donors (n = 5). Significance is indicated (*p < 0.05).
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