title: Radiobiological Effectiveness of Ultrashort Laser-Driven Electron Bunches: Micronucleus Frequency, Telomere Shortening and Cell Viability.
abstract: Laser-driven electron accelerators are capable of producing high-energy electron bunches in shorter distances than conventional radiofrequency accelerators. To date, our knowledge of the radiobiological effects in cells exposed to electrons using a laser-plasma accelerator is still very limited. In this study, we compared the dose-response curves for micronucleus (MN) frequency and telomere length in peripheral blood lymphocytes exposed to laser-driven electron pulse and X-ray radiations. Additionally, we evaluated the effects on cell survival of in vitro tumor cells after exposure to laser-driven electron pulse compared to electron beams produced by a conventional radiofrequency accelerator used for intraoperative radiation therapy. Blood samples from two different donors were exposed to six radiation doses ranging from 0 to 2 Gy. Relative biological effectiveness (RBE) for micronucleus induction was calculated from the alpha coefficients for electrons compared to X rays (RBE = alpha laser/alpha X rays). Cell viability was monitored in the OVCAR-3 ovarian cancer cell line using trypan blue exclusion assay at day 3, 5 and 7 postirradiation (2, 4, 6, 8 and 10 Gy). The RBE values obtained by comparing the alpha values were 1.3 and 1.2 for the two donors. Mean telomere length was also found to be reduced in a significant dose-dependent manner after irradiation with both electrons and X rays in both donors studied. Our findings showed a radiobiological response as mirrored by the induction of micronuclei and shortening of telomere as well as by the reduction of cell survival in blood samples and cancer cells exposed in vitro to laser-generated electron bunches. Additional studies are needed to improve preclinical validation of the radiobiological characteristics and efficacy of laser-driven electron accelerators in the future.
authors.affiliation: a   Genetics Unit, CNR Institute of Clinical Physiology, Pisa, Italy;
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Andreassi
authors.affiliation: a   Genetics Unit, CNR Institute of Clinical Physiology, Pisa, Italy;
authors.forename: Andrea
authors.initials: A
authors.lastname: Borghini
authors.affiliation: a   Genetics Unit, CNR Institute of Clinical Physiology, Pisa, Italy;
authors.forename: Silvia
authors.initials: S
authors.lastname: Pulignani
authors.affiliation: b   Intense Laser Irradiation Laboratory, CNR National Institute of Optics, Pisa, Italy; and.
authors.forename: Federica
authors.initials: F
authors.lastname: Baffigi
authors.affiliation: b   Intense Laser Irradiation Laboratory, CNR National Institute of Optics, Pisa, Italy; and.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Fulgentini
authors.affiliation: b   Intense Laser Irradiation Laboratory, CNR National Institute of Optics, Pisa, Italy; and.
authors.forename: Petra
authors.initials: P
authors.lastname: Koester
authors.affiliation: a   Genetics Unit, CNR Institute of Clinical Physiology, Pisa, Italy;
authors.forename: Monica
authors.initials: M
authors.lastname: Cresci
authors.affiliation: a   Genetics Unit, CNR Institute of Clinical Physiology, Pisa, Italy;
authors.forename: Cecilia
authors.initials: C
authors.lastname: Vecoli
authors.affiliation: c   CNR Institute of Bioimaging and Molecular Physiology, Cefalù (PA), Italy.
authors.forename: Debora
authors.initials: D
authors.lastname: Lamia
authors.affiliation: c   CNR Institute of Bioimaging and Molecular Physiology, Cefalù (PA), Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Russo
authors.affiliation: a   Genetics Unit, CNR Institute of Clinical Physiology, Pisa, Italy;
authors.forename: Daniele
authors.initials: D
authors.lastname: Panetta
authors.affiliation: a   Genetics Unit, CNR Institute of Clinical Physiology, Pisa, Italy;
authors.forename: Maria
authors.initials: M
authors.lastname: Tripodi
authors.affiliation: b   Intense Laser Irradiation Laboratory, CNR National Institute of Optics, Pisa, Italy; and.
authors.forename: Leonida A
authors.initials: LA
authors.lastname: Gizzi
authors.affiliation: b   Intense Laser Irradiation Laboratory, CNR National Institute of Optics, Pisa, Italy; and.
authors.forename: Luca
authors.initials: L
authors.lastname: Labate
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D004583:Electrons; D006801:Humans; D007834:Lasers; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D015162:Micronucleus Tests; D010315:Particle Accelerators; D012062:Relative Biological Effectiveness; D059506:Telomere Shortening / Q000528:radiation effects*; D014965:X-Rays / Q000009:adverse effects