Dose response and kinetics of foci disappearance following exposure to high- and low-LET ionizing radiation

Ugenskienė, Rasa; Prise, Kevin M.; Folkard, M.; Lekki, Janusz; Stachura, Z.; Zazula, Monika; Stachura, Jerzy

doi:10.1080/09553000903072462

Cited by 13 publications

(9 citation statements)

References 44 publications

(32 reference statements)

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“…The mean ± SD of spontaneous 53BP1 foci per cell nucleus in foci-positive cells was 1.29 ± 0.11 foci/cell with a range from 1.04–1.35 foci/cell. These results are consistent with those of Ugenskiene et al , who estimated the background level of 53BP1 foci in AG1522 cells to be 1.1 foci/cell (48). A high background level of nuclear foci indicative of DNA damage was also observed in various cell strains, with inter- and intra-individual differences being detected (47).…”

Section: Methodssupporting

confidence: 92%

Nontargeted Stressful Effects in Normal Human Fibroblast Cultures Exposed to Low Fluences of High Charge, High Energy (HZE) Particles: Kinetics of Biologic Responses and Significance of Secondary Radiations

et al. 2013

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The induction of nontargeted stressful effects in cell populations exposed to low fluences of high charge (Z) and high energy (E) particles is relevant to estimates of the health risks of space radiation. We investigated the up-regulation of stress markers in confluent normal human fibroblast cultures exposed to 1,000 MeV/u iron ions [linear energy transfer (LET) ~151 keV/μm] or 600 MeV/u silicon ions (LET ~50 keV/μm) at mean absorbed doses as low as 0.2 cGy, wherein 1–3% of the cells were targeted through the nucleus by a primary particle. Within 24 h postirradiation, significant increases in the levels of phospho-TP53 (serine 15), p21Waf1 (CDKN1A), HDM2, phospho-ERK1/2, protein carbonylation and lipid peroxidation were detected, which suggested participation in the stress response of cells not targeted by primary particles. This was supported by in situ studies that indicated greater increases in 53BP1 foci formation, a marker of DNA damage. than expected from the number of primary particle traversals. The effect was expressed as early as 15 min after exposure, peaked at 1 h and decreased by 24 h. A similar tendency occurred after exposure of the cell cultures to 0.2 cGy of 3.7 MeV α particles (LET ~109 keV/μm) that targets ~1.6% of nuclei, but not after 0.2 cGy from 290 MeV/u carbon ions (LET ~13 keV/μm) by which, on average, ~13% of the nuclei were hit, which highlights the importance of radiation quality in the induced effect. Simulations with the FLUKA multi-particle transport code revealed that fragmentation products, other than electrons, in cell cultures exposed to HZE particles comprise <1% of the absorbed dose. Further, the radial spread of dose due to secondary heavy ion fragments is confined to approximately 10–20 μm. Thus, the latter are unlikely to significantly contribute to stressful effects in cells not targeted by primary HZE particles.

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Section: Methodssupporting

confidence: 92%

Nontargeted Stressful Effects in Normal Human Fibroblast Cultures Exposed to Low Fluences of High Charge, High Energy (HZE) Particles: Kinetics of Biologic Responses and Significance of Secondary Radiations

et al. 2013

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“…The DNA lesions described here appear to be of a different nature. In the case of heavy ions clustered DNA damage is created by high ionization density along the primary particle path262728293031. High LET radiation can also cause damage over larger distances (i.e.…”

Section: Discussionmentioning

confidence: 99%

Antiproton induced DNA damage: proton like in flight, carbon-ion like near rest

Kavanagh

Currell

Timson

et al. 2013

Sci Rep

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Biological validation of new radiotherapy modalities is essential to understand their therapeutic potential. Antiprotons have been proposed for cancer therapy due to enhanced dose deposition provided by antiproton-nucleon annihilation. We assessed cellular DNA damage and relative biological effectiveness (RBE) of a clinically relevant antiproton beam. Despite a modest LET (~19 keV/μm), antiproton spread out Bragg peak (SOBP) irradiation caused significant residual γ-H2AX foci compared to X-ray, proton and antiproton plateau irradiation. RBE of ~1.48 in the SOBP and ~1 in the plateau were measured and used for a qualitative effective dose curve comparison with proton and carbon-ions. Foci in the antiproton SOBP were larger and more structured compared to X-rays, protons and carbon-ions. This is likely due to overlapping particle tracks near the annihilation vertex, creating spatially correlated DNA lesions. No biological effects were observed at 28–42 mm away from the primary beam suggesting minimal risk from long-range secondary particles.

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“…type of radiations including low linear energy transfer (LET) X-rays [87], protons and high LET ions such as silicon, iron [88] and carbon ions [89,90]. Subsequently, additional biomarkers related to γ-H2AX were also identified which phosphorylate in the close proximity of DNA DSB.…”

Section: Dna Double Strand Break (Dsb) Damagementioning

confidence: 99%

Radiobiology Experiments With Ultra-high Dose Rate Laser-Driven Protons: Methodology and State-of-the-Art

Chaudhary¹,

Milluzzo

Ahmed

et al. 2021

Front. Phys.

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The use of particle accelerators in radiotherapy has significantly changed the therapeutic outcomes for many types of solid tumours. In particular, protons are well known for sparing normal tissues and increasing the overall therapeutic index. Recent studies show that normal tissue sparing can be further enhanced through proton delivery at 100 Gy/s and above, in the so-called FLASH regime. This has generated very significant interest in assessing the biological effects of proton pulses delivered at very high dose rates. Laser-accelerated proton beams have unique temporal emission properties, which can be exploited to deliver Gy level doses in single or multiple pulses at dose rates exceeding by many orders of magnitude those currently used in FLASH approaches. An extensive investigation of the radiobiology of laser-driven protons is therefore not only necessary for future clinical application, but also offers the opportunity of accessing yet untested regimes of radiobiology. This paper provides an updated review of the recent progress achieved in ultra-high dose rate radiobiology experiments employing laser-driven protons, including a brief discussion of the relevant methodology and dosimetry approaches.

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Dose response and kinetics of foci disappearance following exposure to high- and low-LET ionizing radiation

Cited by 13 publications

References 44 publications

Nontargeted Stressful Effects in Normal Human Fibroblast Cultures Exposed to Low Fluences of High Charge, High Energy (HZE) Particles: Kinetics of Biologic Responses and Significance of Secondary Radiations

Nontargeted Stressful Effects in Normal Human Fibroblast Cultures Exposed to Low Fluences of High Charge, High Energy (HZE) Particles: Kinetics of Biologic Responses and Significance of Secondary Radiations

Antiproton induced DNA damage: proton like in flight, carbon-ion like near rest

Radiobiology Experiments With Ultra-high Dose Rate Laser-Driven Protons: Methodology and State-of-the-Art

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