naa a22 4500 510764045 CHVBK 20180411083150.0 cr unu---uuuuu 180411e20130401xx s 000 0 eng 10.1007/s12094-012-0917-9 doi (NATIONALLICENCE)springer-10.1007/s12094-012-0917-9 Zoledronic acid and radiation: toxicity, synergy or radiosensitization? [Elektronische Daten] [M. Alcaraz, A. Olivares, D. Armero, M. Alcaraz-Saura, D. Achel] Introduction: Zoledronic acid (Z) is a bisphosphonate used in hypercalcaemia-related cancer, in complications for bone metastasis and in postmenopausal osteoporosis and it has been related to osteoradionecrosis, especially when associated with radiation to the head and neck structures. Objectives: To determine the radiosensitization capacity of zoledronic acid in the combined treatment with ionizing radiation (IR) by evaluating its genotoxic and cytotoxic capacities in non-tumoral cells. Materials and methods: The genotoxic effect of Z was studied by means of the micronucleus test in cytokinesis-blocked cells of human lymphocytes irradiated before and after a 2Gy irradiation, while the cytotoxic effect was studied by a cell viability test in the PNT2 cell line before and after exposure to different X-ray doses (0-20Gy) in four groups (Z alone, radiation alone, Z+IR and IR+Z). Results: A dose-dependent and time-dependent cytotoxic effect of Z and IR on PNT2 cells in vitro (p>0.001) was demonstrated. With the concentrations recommended for humans, the combined treatment had a more pronounced effect than individual treatments (p<0.001). The effect was synergic (CI<1), increasing the Z enhancement ratio (2.6) and sensitization factor (56%); the effect of Z was always greater after IR exposure. In the genotoxic effect, only the administration of Z after irradiation (IR+Z) increased chromosome damage (p<0.001) and the sensibilization factor (35.7%). Conclusion: High concentrations of Z are toxic, but the concentrations recommended for clinical practice in humans give it the characteristics of a radiosensitization agent, whose effect is even greater when administered after IR. Federación de Sociedades Españolas de Oncología (FESEO), 2012 Radiosensitivity nationallicence Zoledronic acid nationallicence Synergism nationallicence Radiation effects nationallicence Bisphosphonates nationallicence Alcaraz M. Radiology and Physical Medicine Department, Faculty of Medicine/Dentistry, University of Murcia, Campus de Espinardo, 30100, Murcia, Spain aut Olivares A. Radiology and Physical Medicine Department, Faculty of Medicine/Dentistry, University of Murcia, Campus de Espinardo, 30100, Murcia, Spain aut Armero D. Nursing Department, Faculty of Nursing, University of Murcia, Campus de Espinardo, 30100, Murcia, Spain aut Alcaraz-Saura M. Radiology and Physical Medicine Department, Faculty of Medicine/Dentistry, University of Murcia, Campus de Espinardo, 30100, Murcia, Spain aut Achel D. Applied Radiation Biology Centre, Radiological and Medical Sciences Research Institute, Ghana Atomic Energy Commission, Legon-Accra, Ghana aut Clinical and Translational Oncology Springer Milan 15/4(2013-04-01), 300-306 1699-048X 15:4<300 2013 15 12094 https://doi.org/10.1007/s12094-012-0917-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12094-012-0917-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Alcaraz M. Radiology and Physical Medicine Department, Faculty of Medicine/Dentistry, University of Murcia, Campus de Espinardo, 30100, Murcia, Spain aut NATIONALLICENCE 700 1- Olivares A. Radiology and Physical Medicine Department, Faculty of Medicine/Dentistry, University of Murcia, Campus de Espinardo, 30100, Murcia, Spain aut NATIONALLICENCE 700 1- Armero D. Nursing Department, Faculty of Nursing, University of Murcia, Campus de Espinardo, 30100, Murcia, Spain aut NATIONALLICENCE 700 1- Alcaraz-Saura M. Radiology and Physical Medicine Department, Faculty of Medicine/Dentistry, University of Murcia, Campus de Espinardo, 30100, Murcia, Spain aut NATIONALLICENCE 700 1- Achel D. Applied Radiation Biology Centre, Radiological and Medical Sciences Research Institute, Ghana Atomic Energy Commission, Legon-Accra, Ghana aut NATIONALLICENCE 773 0- Clinical and Translational Oncology Springer Milan 15/4(2013-04-01), 300-306 1699-048X 15:4<300 2013 15 12094 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer