Radiobiological Effectiveness of Ultrashort Laser-Driven Electron Bunches: Micronucleus Frequency, Telomere Shortening and Cell Viability

Andreassi, Maria Grazia; Borghini, Andrea; Pulignani, Silvia; Baffigi, F.; Fulgentini, Lorenzo; Koester, P.; Cresci, Monica; Vecoli, Cecilia; Lamia, Debora; Russo, Giorgio; Panetta, Daniele; Tripodi, Maria; Gizzi, L. A.; Labate, L.

doi:10.1667/rr14266.1

Cited by 23 publications

(21 citation statements)

References 36 publications

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“…Laser‐plasma accelerators produce femtosecond electron bunches that are quasi mono‐energetic with energies in the range of tens of MeV up to a few GeV, and with a pulsed dose‐rate exceeding 10 13 Gy/s. Results have been recently reported on biological material irradiated with laser generated electrons both in vitro and in vivo. …”

Section: High Dose‐rate Radiation Sourcesmentioning

confidence: 99%

“…Laser-plasma accelerators produce femtosecond electron bunches 51 that are quasi mono-energetic with energies in the range of tens of MeV up to a few GeV, and with a pulsed dose-rate exceeding 10 13 Gy/s. Results have been recently reported on biological material irradiated with laser generated electrons both in vitro 52,53 and in vivo. 54,55 In order to destroy tumor cells that adapt to radiation, synergy between the effects of subsequent pulses or different types of radiation is taken into consideration in complex radiotherapy-oriented studies.…”

Section: B Beyond Laser-generated Protons: Heavy Ions and Other Tymentioning

confidence: 99%

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Laser‐driven radiation: Biomarkers for molecular imaging of high dose‐rate effects

et al. 2019

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Recently developed short‐pulsed laser sources garner high dose‐rate beams such as energetic ions and electrons, x rays, and gamma rays. The biological effects of laser‐generated ion beams observed in recent studies are different from those triggered by radiation generated using classical accelerators or sources, and this difference can be used to develop new strategies for cancer radiotherapy. High‐power lasers can now deliver particles in doses of up to several Gy within nanoseconds. The fast interaction of laser‐generated particles with cells alters cell viability via distinct molecular pathways compared to traditional, prolonged radiation exposure. The emerging consensus of recent literature is that the differences are due to the timescales on which reactive molecules are generated and persist, in various forms. Suitable molecular markers have to be adopted to monitor radiation effects, addressing relevant endogenous molecules that are accessible for investigation by noninvasive procedures and enable translation to clinical imaging. High sensitivity has to be attained for imaging molecular biomarkers in cells and in vivo to follow radiation‐induced functional changes. Signal‐enhanced MRI biomarkers enriched with stable magnetic nuclear isotopes can be used to monitor radiation effects, as demonstrated recently by the use of dynamic nuclear polarization (DNP) for biomolecular observations in vivo. In this context, nanoparticles can also be used as radiation enhancers or biomarker carriers. The radiobiology‐relevant features of high dose‐rate secondary radiation generated using high‐power lasers and the importance of noninvasive biomarkers for real‐time monitoring the biological effects of radiation early on during radiation pulse sequences are discussed.

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Section: High Dose‐rate Radiation Sourcesmentioning

confidence: 99%

Section: B Beyond Laser-generated Protons: Heavy Ions and Other Tymentioning

confidence: 99%

Laser‐driven radiation: Biomarkers for molecular imaging of high dose‐rate effects

et al. 2019

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“…Recent achievements in the field of particle acceleration technologies has led to development of cost- and size-effective laser-driven electron accelerators (LDEAs) [11, 12]. This technology permits to deliver high energy beams (from few MeV up to several hundred MeV) into deep layers of tissue in pico- or femtosecond durations with little lateral spread [13–15].…”

Section: Introductionmentioning

confidence: 99%

“…Studies of the genetic effects of accelerated particles are still limited. Recently genetic effects of irradiation with LDEA were estimated using comet assay [29, 30], micronucleus test [12] and gammaH2AX foci, reflecting level of DSBs [16, 31, 32]. But for all we know, the effect of accelerated particles on CNVs has not yet been studied.…”

Section: Introductionmentioning

confidence: 99%

Analysis of copy number variations induced by ultrashort electron beam radiation in human leukocytes in vitro

et al. 2019

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Background Environmental risk factors have been shown to alter DNA copy number variations (CNVs). Recently, CNVs have been described to arise after low-dose ionizing radiation in vitro and in vivo. Development of cost- and size-effective laser-driven electron accelerators (LDEAs), capable to deliver high energy beams in pico- or femtosecond durations requires examination of their biological effects. Here we studied in vitro impact of LDEAs radiation on known CNV hotspots in human peripheral blood lymphocytes on single cell level. Results Here CNVs in chromosomal regions 1p31.1, 7q11.22, 9q21.3, 10q21.1 and 16q23.1 earlier reported to be sensitive to ionizing radiation were analyzed using molecular cytogenetics. Irradiation of cells with 0.5, 1.5 and 3.0 Gy significantly increased signal intensities in all analyzed chromosomal regions compared to controls. The latter is suggested to be due to radiation-induced duplication or amplification of CNV stretches. As significantly lower gains in mean fluorescence intensities were observed only for chromosomal locus 1p31.1 (after irradiation with 3.0 Gy variant sensitivites of different loci to LDEA is suggested. Negative correlation was found between fluorescence intensities and chromosome size ( r = − 0.783, p < 0.001) in cells exposed to 3.0 Gy irradiation and between fluorescence intensities and gene density ( r = − 0.475, p < 0.05) in cells exposed to 0.5 Gy irradiation. Conclusions In this study we demonstrated that irradiation with laser-driven electron bunches can induce molecular-cytogenetically visible CNVs in human blood leukocytes in vitro. These CNVs occur most likely due to duplications or amplification and tend to inversely correlate with chromosome size and gene density. CNVs can last in cell population as stable chromosomal changes for several days after radiation exposure; therefore this endpoint can be used for characterization of genetic effects of accelerated electrons. These findings should be complemented with other studies and implementation of more sophisticated approaches for CNVs analysis.

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“…Moreover, the extremely short duration of LPA bunches allows possible novel phenomena in radiobiology to be investigated, possibly gaining access to the very early phase of the damage induced on a particular cell structure by the primary ionizing particle 58 . Several works have been reported in the field over the past decade 50,59,60 .…”

mentioning

confidence: 99%

Toward an effective use of laser-driven very high energy electrons for radiotherapy: Feasibility assessment of multi-field and intensity modulation irradiation schemes

Labate

Palla

Panetta

et al. 2020

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Radiotherapy with very high energy electrons has been investigated for a couple of decades as an effective approach to improve dose distribution compared to conventional photon-based radiotherapy, with the recent intriguing potential of high dose-rate irradiation. Its practical application to treatment has been hindered by the lack of hospital-scale accelerators. High-gradient laser-plasma accelerators (LPA) have been proposed as a possible platform, but no experiments so far have explored the feasibility of a clinical use of this concept. We show the results of an experimental study aimed at assessing dose deposition for deep seated tumours using advanced irradiation schemes with an existing LPA source. Measurements show control of localized dose deposition and modulation, suitable to target a volume at depths in the range from 5 to 10 cm with mm resolution. The dose delivered to the target was up to 1.6 Gy, delivered with few hundreds of shots, limited by secondary components of the LPA accelerator. Measurements suggest that therapeutic doses within localized volumes can already be obtained with existing LPA technology, calling for dedicated pre-clinical studies.

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Radiobiological Effectiveness of Ultrashort Laser-Driven Electron Bunches: Micronucleus Frequency, Telomere Shortening and Cell Viability

Cited by 23 publications

References 36 publications

Laser‐driven radiation: Biomarkers for molecular imaging of high dose‐rate effects

Laser‐driven radiation: Biomarkers for molecular imaging of high dose‐rate effects

Analysis of copy number variations induced by ultrashort electron beam radiation in human leukocytes in vitro

Toward an effective use of laser-driven very high energy electrons for radiotherapy: Feasibility assessment of multi-field and intensity modulation irradiation schemes

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