Biological effects and inter-individual variability in peripheral blood lymphocytes of healthy donors exposed to 60 MeV proton radiotherapeutic beam

Abstract

Purpose: The aim of our study was to investigate the amount of initial DNA damage and cellular repair capacity of human peripheral blood lymphocytes exposed to the therapeutic proton beam and compare it to X-rays.

Materials and methods: Lymphocytes from 10 healthy donors were irradiated in the Spread Out Bragg Peak of the 60 MeV proton beam or, as a reference, exposed to 250 kV X-rays. DNA damage level was assessed using the alkaline version of the comet assay method. For both sources of radiation, dose–DNA damage response (0–4 Gy) and DNA repair kinetics (0–120 min) were estimated. The observed DNA damage was then used to calculate the relative biological effectiveness (RBE) of the proton beam in comparison to that of X-rays.

Results: Dose–response relationships for the DNA damage level showed linear dependence for both proton beam and X-rays (R² = 0.995 for protons and R² = 0.993 for X-rays). Within the dose range of 1–4 Gy, protons were significantly more effective in inducing DNA damage than were X-rays (p < .05). The average RBE, calculated from the proton and X-ray doses required for the iso-effective, internally standardized tail DNA parameter (sT-DNA) was 1.28 ± 0.57. Similar half-life time of residual damage and repair efficiency of induced DNA damage for both radiation types were observed. In the X-irradiated group, significant inter-individual differences were observed.

Conclusions: Proton therapy was more effective at high radiation doses. However, DNA damage repair mechanism after proton irradiation seems to differ from that following X-rays.

Keywords:

• Protons
• X-rays
• DNA damage response/repair
• RBE

Acknowledgments

A crucially valuable discussion, comments, and suggestions by Mr. Wojciech Zając are highly appreciated.

Disclosure statement

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

Additional information

Funding

These investigations were partially supported by grants DEC-2017/01/X/NZ7/00426 and DEC-2013/09/D/NZ7/00324 from the National Science Centre, Poland.

Notes on contributors

Agnieszka Panek

Agnieszka Panek, PhD, specialist at the Department of Experimental Physics of Complex Systems, IFJ PAN. Her research focuses on the biological mechanisms of particle radiotherapy, in particular on the processes of DNA damage repair, cell cycle and apoptosis.

Justyna Miszczyk

Justyna Miszczyk, PhD, assistant professor at the Department of Experimental Physics of Complex Systems, IFJ PAN. Her research focuses on the biological mechanisms of particle radiotherapy, characterizing the response of different kinds of cancer/normal cells to this promising treatment modality with the goal of improving therapeutic benefit.

Jan Swakoń

Jan Swakoń, PhD, head of the Proton Radiotherapy Group at the Division of Applied Physics at IFJ PAN. The main scientific activity focuses on proton radiotherapy, dosimetry and medical physics. Experience in radiation physics and dosimetry, environmental physics, nuclear geophysics, radiobiology and technical physics.