Monte Carlo Modeling of DNA Lesions and Chromosomal Aberrations Induced by Mixed Beams of Alpha Particles and X-Rays

Brzozowska, B.; Tartas, Adrianna; Wójcik, Andrzej

doi:10.3389/fphy.2020.567864

Cited by 6 publications

(3 citation statements)

References 34 publications

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“…The results of experiments with different cell types and different endpoints quite consistently show that the effect of combined exposure to alpha particles and X-rays is stronger than expected based on simple additivity [ 37 – 44 ]. The experimental results were confirmed by Monte Carlo simulations performed with the PARTRAC tool [ 45 ]. However, the mechanisms responsible for the interaction remain largely enigmatic.…”

Section: Introductionmentioning

confidence: 79%

The order of sequential exposure of U2OS cells to gamma and alpha radiation influences the formation and decay dynamics of NBS1 foci

Tartas¹,

Lundholm²,

Scherthan³

et al. 2023

PLoS ONE

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DNA double strand breaks (DSBs) are a deleterious form of DNA damage. Densely ionising alpha radiation predominantly induces complex DSBs and sparsely ionising gamma radiation—simple DSBs. We have shown that alphas and gammas, when applied simultaneously, interact in producing a higher DNA damage response (DDR) than predicted by additivity. The mechanisms of the interaction remain obscure. The present study aimed at testing whether the sequence of exposure to alphas and gammas has an impact on the DDR, visualised by live NBS1-GFP (green fluorescent protein) focus dynamics in U2OS cells. Focus formation, decay, intensity and mobility were analysed up to 5 h post exposure. Focus frequencies directly after sequential alpha → gamma and gamma → alpha exposure were similar to gamma alone, but gamma → alpha foci quickly declined below the expected values. Focus intensities and areas following alpha alone and alpha → gamma were larger than after gamma alone and gamma → alpha. Focus movement was most strongly attenuated by alpha → gamma. Overall, sequential alpha → gamma exposure induced the strongest change in characteristics and dynamics of NBS1-GFP foci. Possible explanation is that activation of the DDR is stronger when alpha-induced DNA damage precedes gamma-induced DNA damage.

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Section: Introductionmentioning

confidence: 79%

The order of sequential exposure of U2OS cells to gamma and alpha radiation influences the formation and decay dynamics of NBS1 foci

Tartas¹,

Lundholm²,

Scherthan³

et al. 2023

PLoS ONE

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“…Interestingly, the impairment of the repair machinery by high-LET radiation, which increases damage complexity, could also be at the basis of a possible synergistic action of high- and low-LET components in mixed radiation fields. Recently, this was investigated with experimental measurements of chromosomal aberrations in human peripheral blood lymphocytes exposed to mixed beams consisting of equal contributions of alpha particles and X-rays (Brzozowska et al 2020 ).…”

Section: Patterns Of Radiation-induced Dna Damage: Interactions At Di...mentioning

confidence: 99%

A matter of space: how the spatial heterogeneity in energy deposition determines the biological outcome of radiation exposure

Baiocco

Bartzsch

Conte

et al. 2022

Radiat Environ Biophys

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The outcome of the exposure of living organisms to ionizing radiation is determined by the distribution of the associated energy deposition at different spatial scales. Radiation proceeds through ionizations and excitations of hit molecules with an ~ nm spacing. Approaches such as nanodosimetry/microdosimetry and Monte Carlo track-structure simulations have been successfully adopted to investigate radiation quality effects: they allow to explore correlations between the spatial clustering of such energy depositions at the scales of DNA or chromosome domains and their biological consequences at the cellular level. Physical features alone, however, are not enough to assess the entity and complexity of radiation-induced DNA damage: this latter is the result of an interplay between radiation track structure and the spatial architecture of chromatin, and further depends on the chromatin dynamic response, affecting the activation and efficiency of the repair machinery. The heterogeneity of radiation energy depositions at the single-cell level affects the trade-off between cell inactivation and induction of viable mutations and hence influences radiation-induced carcinogenesis. In radiation therapy, where the goal is cancer cell inactivation, the delivery of a homogenous dose to the tumour has been the traditional approach in clinical practice. However, evidence is accumulating that introducing heterogeneity with spatially fractionated beams (mini- and microbeam therapy) can lead to significant advantages, particularly in sparing normal tissues. Such findings cannot be explained in merely physical terms, and their interpretation requires considering the scales at play in the underlying biological mechanisms, suggesting a systemic response to radiation.

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“…In addition to the differences between high-LET and low-LET radiation, there are conflicting results on whether irradiation of cells with low-LET radiation before high-LET radiation, as would occur in a space environment, has a synergistic or protective effect on DNA damage. Most researchers have stated there is a detrimental effect of pre-irradiation with low-LET radiation followed by high-LET radiation, with peak chromosomal damage at a 30-min interval between the irradiation regimes [ 68 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 ]. However, Buonanno et al [ 87 , 88 ] and Stoilov et al [ 87 , 88 ] have observed a protective effect if the interval is up to 24 h, with researchers attributing this effect to the upregulation of redox scavengers of antioxidants.…”

Section: General Effects Of Radiation On Dna/cancer Cellsmentioning

confidence: 99%

Cancer Studies under Space Conditions: Finding Answers Abroad

et al. 2021

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In this review article, we discuss the current state of knowledge in cancer research under real and simulated microgravity conditions and point out further research directions in this field. Outer space is an extremely hostile environment for human life, with radiation, microgravity, and vacuum posing significant hazards. Although the risk for cancer in astronauts is not clear, microgravity plays a thought-provoking role in the carcinogenesis of normal and cancer cells, causing such effects as multicellular spheroid formation, cytoskeleton rearrangement, alteration of gene expression and protein synthesis, and apoptosis. Furthermore, deleterious effects of radiation on cells seem to be accentuated under microgravity. Ground-based facilities have been used to study microgravity effects in addition to laborious experiments during parabolic flights or on space stations. Some potential ‘gravisensors’ have already been detected, and further identification of these mechanisms of mechanosensitivity could open up ways for therapeutic influence on cancer growth and apoptosis. These novel findings may help to find new effective cancer treatments and to provide health protection for humans on future long-term spaceflights and exploration of outer space.

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Monte Carlo Modeling of DNA Lesions and Chromosomal Aberrations Induced by Mixed Beams of Alpha Particles and X-Rays

Cited by 6 publications

References 34 publications

The order of sequential exposure of U2OS cells to gamma and alpha radiation influences the formation and decay dynamics of NBS1 foci

The order of sequential exposure of U2OS cells to gamma and alpha radiation influences the formation and decay dynamics of NBS1 foci

A matter of space: how the spatial heterogeneity in energy deposition determines the biological outcome of radiation exposure

Cancer Studies under Space Conditions: Finding Answers Abroad

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