Relation between DNA double-strand breaks and energy spectra of secondary electrons produced by different X-ray energies

Abstract

Purpose: In a radiological examination, low-energy X-radiation is used (<100 keV). For other radiological procedures, the energy used is several MeV. ICRP in publication 103 has currently considered that photons irrespective of their energy have the same radiation weighting factor. Nevertheless, there are topological differences at the nanoscale of X-ray energy deposition as a function of its energy spectrum, meaning that the different interactions with living matter could vary in biological efficacy.

Materials and methods: To study these differences, we characterized our irradiation conditions in terms of initial photon energies, but especially in terms of energy spectra of secondary electrons at the cell nucleus level, using Monte Carlo simulations. We evaluated signaling of DNA damage by monitoring a large number of γH2A.X foci after exposure of G0/G1-phase synchronized human primary endothelial cells from 0.25 to 5 Gy at 40 kV, 220 kV and 4 MV X-rays. Number and spatial distribution of γH2A.X foci were explored. In parallel, we investigated cell behavior through cell death and ability of a mother cell to produce two daughter cells. We also studied the missegregation rate after cell division.

Results: We report a higher number of DNA double-strand breaks signaled by γH2A.X for 40 kVp and/or 220 kVp compared to 4 MVp for the highest tested doses of 2 and 5 Gy. We observed no difference between the biological endpoint studies with 40 kVp and 220 kVp X-ray spectra. This lack of difference could be explained by the relative similarity of the calculated energy spectra of secondary electrons at the cell monolayer.

Conclusion: The energy spectrum of secondary electrons seems to be more closely related to the level of DNA damage measured by γH2A.X than the initial spectrum of photon energy or voltage settings. Our results indicate that as the energy spectrum of secondary electrons increases, the DNA damage signaled by γH2A.X decreases and this effect is observable beyond 220 kVp.

Keywords:

• Energy X-rays
• secondary electrons
• DNA damage
• γH2A.X foci
• cell behavior
• missegregation

Acknowledgments

The authors would like to thank Y. Ristic for performing the radiation exposure with the Elekta Synergy accelerator.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Notes on contributors

Amelie Freneau

Amélie Fréneau is a PhD student in the field of radiation biology at IRSN. She focuses on studying biological effects of endothelial cells exposed to different energies of X-rays

Morgane Dos Santos

Morgane Dos Santos is a researcher in physics who focuses her work on dosimetry and in charge of the SARRP platform at IRSN.

Pascale Voisin

Pascale Voisin is a technician specialized in radiation biology and cytogenetic.

Nicolas Tang

Nicolas Tang is a PhD student in the field of Monte Carlo simulation of ionizing radiation.

Marta Bueno Vizcarra

Marta Bueno Vizcarra is a researcher in physics focusing on Monte Carlo simulation of ionizing radiation.

Carmen Villagrasa

Carmen Villagrasa is the head of the Ionizing Radiation Dosimetry Laboratory (LDRI) at IRSN. She studies the interaction mechanism of ionizing radiation with biological targets (DNA in particular) in order to calculate early biological damages using Monte Carlo methods. She is a member of the Geant4 and the Geant4-DNA collaborations.

Laurence Roy

Laurence Roy is deputy director of the Department of Research on the Biological and Health Effects of Ionizing Radiation.

Aurelie Vaurijoux

Aurelie Vaurijoux is a researcher in biology focusing on the signalization of DNA damage.

Gaetan Gruel

Gaetan Gruel is the head of the Radiobiology of Accidental Exposure Laboratory (LRAcc) at IRSN. He studies the effects of different exposure scenarios (dose and dose rate, nature and energy of the radiation) on the molecular components of cells (including DNA) and their consequences at cell level. He works more specifically on establishing links between micro and nano-dosimetric quantities with biological effects.