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

Year: 2016

Authors: Andreassi M.G., Borghini A., Pulignani S., Baffigi F., Fulgentini L., Koester P., Cresci M., Vecoli C., Lamia D., Russo G., Panetta D., Tripodi M., Gizzi L.A., Labate L.

Autors Affiliation: Genetics Unit, CNR Institute of Clinical Physiology, via Moruzzi 1, Pisa, 56124, Italy; Intense Laser Irradiation Laboratory, CNR National Institute of Optics, Pisa, Italy; CNR Institute of Bioimaging and Molecular Physiology, Cefalù (PA), Italy

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.


Volume: 186 (3)      Pages from: 245  to: 253

More Information: PRIN2012AY5LEL. GR-2009-1608935. – Laser radiation experiments were performed at the Intense Laser Irradiation Laboratory of the INO-CNR Section in Pisa, Italy. The work of the INO-CNR Pisa group was partially supported by the Italian Ministry of Health (project no. GR-2009-1608935: Study of Radiobiological and Radiotherapeutic Effects of a Novel Laser-Driven Electron Accelerator, D.I. AgeNaS), from the CNR-funded Italian Research Network ELIItaly (Attoseconds) and from the PRIN project (contract no. PRIN2012AY5LEL). The Pisa authors also acknowledge contributions by the MIUR-FIRB project SPARX (Sorgente Pulsata Auto-Amplificata di Radiazione X) and the INFN Plasma-Med collaboration. We thank Dr. Fabio Di Martino, U.O. Health Physics, Azienda Ospedaliero-Universitaria Pisana (Pisa, Italy) for use of the intraoperative radiation therapy facility.
KeyWords: Blood sampling; Cell proliferation; Cell survival; Cell viability; Cell viability assay; Controlled study; Electron accelerator; Electron beam; female; human; human cell; intraoperative radiotherapy; laser; laser driven electron accelerator; linear accelerator; male; micronucleus; normal human; ovarian cancer cell line; peripheral lymphocyte; priority journal; radiation response; radiobiology; radiofrequency radiation; radiotherapy dosage; telomere length; telomere shortening; adverse effects; cytology; electron; lymphocyte; magnetic and electromagnetic equipment; metabolism; micronucleus test; relative biologic effectiveness; telomere shortening; tumor cell line; X ray, Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Radiation; Electrons; Humans; Lasers; Lymphocytes; Micronucleus Tests; Particle Accelerators; Relative Biological Effectiveness; Telomere Shortening; X-Rays
DOI: 10.1667/RR14266.1

Citations: 19
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