Research topics

Radiation biology of the cell: application in therapy and protection

  • Associates:
  • Associates from abroad and/or external associates: Dr Ivan Petrović, NSV
    Dr Miloš Đorđević, VNS (010)
    Dr Giacomo Cuttone, INFN – LNS
    Dr G.A.P. Cirrone, INFN – LNS
    Dr Giada Petringa, INFN – LNS
    Dr Sebastien Incerti, CENBG, CNRS/IN2P3/Université Bordeaux 1
  • Research Summary:

    Using a multidisciplinary approach in research, combined with the knowledge from the fields of biology, physics and medicine, the direct and indirect effects of ionizing radiation on normal and human cancer cells are examined. In addition to conventional gamma radiation, most of the research relates to the effects of highly ionizing radiation, such as protons and carbon ions used in cancer therapy, as well as helium and oxygen ions. Innovative in vitro studies of the effects of FLASH radiotherapy are also planned, which represent the use of extremely high dose rates (≥ 40 Gy / s) for irradiation of tumor tissue that simultaneously protects the surrounding healthy tissue.

    In addition, radiosensitization of cells using gold nanoparticles (AuNP) will be investigated, as well as the combined effects of radiation and chemotherapeutic agents and new agents used in targeted molecular therapy (anti-EGFR therapy). The main goal of research is to examine the cellular response to damage caused by conventional and highly ionizing radiation, as well as the improvement of modern therapeutic protocols. DNA damage response (DDR) is monitored using biological parameters, such as cell cycle changes, expression of certain genes involved in the DDR cascade, and the occurrence of various forms of cell death (apoptosis, senescence, and autophagy). Formation of phosphorylated H2AX nuclei (γ-H2AX) at sites of DNA double-strand breaks, in addition to clonogenic survival, which is the "gold standard" in radiation biology, is used as a biomarker for rapid detection and monitoring of cellular radiosensitivity in preclinical studies and in clinics.

    In addition, the group is a member of the recently established international collaboration in the field of biophysics initiated by GSI, as well as the collaboration under the auspices of CERN, which is based on comparison and interpretation of experimental results using the numerical simulation tool GEANT4 (GEometry ANd Tracking) GEANT4-DNA extension. All these activities aim to improve modern therapeutic protocols for the treatment of certain types of cancer.
  • Projects on the Topic:
    • 2021 - 23 Project Ideje: Utilization of interplay between inflammation and cancer in the development of compounds with anticancer activity, participant Dr Otilija Keta, Assiatant Research Professor.
    • 2021 - 23 ESA multilateral project EXPRO+ /BioRad3, AO-1-10318.
    • 2019 - 22 Project Grande Rilevanza nо. PGR00794 (Progetto di Grande Rilevanza, MAECI – Ministero degli Affari Esteri e della Cooperazione Internationale, Italy), within the framework of the Executive Programm of Scientific and Technological Cooperation between Republic of Italy and Republic of Serbia.
    • 2018 - 21 International collaboration with CNBG/IN2P3/CNRS/ Université Bordeaux 1 (Projets international de coopération scientifique – PICS, CNRS, No 8070), France
    • 2016 - 21 European Commission Project, ENSAR2 (European Nuclear Science and Applications Research2), Transnational Access Activities (TNAs). Grant Agreement: nо. 654002
    • 2016 - 21 European Commission Project, ENSAR2 (European Nuclear Science and Applications Research2), Networking Activities (NAs). Grant Agreement: nо. 654002
    • 2014 - .. GEANT4-DNA Collaboration (coordinated by CENBG since 2008)
    • 2009 - .. GEANT4 Collaboration, Low Energy Electromagnetic Working Group and Advanced Examples Working Group, Organisation Européenne pour la Recherche Nucléaire – CERN, Switzerland
  • Publications:
    1. M. Scholz, T. Friedrich, G. Magrin, P. Colautti, A. Ristić-Fira, I. Petrović. Characterizing radiation effectiveness in ion beam therapy, Characterizing radiation effectiveness in ion beam therapy, Part I: Introduction and Biophysical Modelling of RBE using the LEMIV, Frontiers in Physics - Medical Physics and Imaging: Applied Nuclear Physics at Accelerators, 2020, 8:272, https://doi.org/10.3389/fphy.2020.00272
    2. A. Ristic Fira, O. Keta, V. Petkovic, F. Cammarata, G. Petringa, G.A.P. Cirrone, G. Cuttone, S. Incerti, I. Petrovic. DNA damage assessment of human breast and lung carcinoma cells irradiated with protons and carbon ions. Journal of Radiation Research and Applied Sciences, 2020, 13 (1), 672-687, https://doi.org/10.1080/16878507.2020.1825035
    3. Dousatsu Sakata, Oleg Belov, Marie-Claude Bordage, Dimitris Emfietzoglou, Susanna Guatelli, Taku Inaniwa, Vladimir Ivanchenko, Mathieu Karamitros, Ioanna Kyriakou, Nathanael Lampe, Ivan Petrovic, Aleksandra Ristic-Fira, Wook-Geun Shin, Sebastien Incerti. Fully integrated Monte Carlo simulation for evaluating radiation induced DNA damage and following repair using Geant4-DNA. Scientific Reports, 2020, 10, 20788, https://doi.org/10.1038/s41598-020-75982-x
    4. Ivan M. Petrović, Aleksandra M. Ristić Fira, Otilija D. Keta, Vladana D. Petković, Giada Petringa, Pablo Cirrone, Giacomo Cuttone. A Radiobiological Study of Carbon Ions of Different Linear Energy Transfer in Resistant Human Malignant Cell Lines. International Journal of Radiation Biology, 2020, 96 (11), 1400-1412, https://doi.org/10.1080/09553002.2020.1820609
    5. Otilija Keta, Vladana Petković, Pablo Cirrone, Giada Petringa, Giacomo Cuttone, Dousatsu Sakata, Wook-Geun Shin, Sebastien Incerti, Ivan Petrović and Aleksandra Ristić Fira. DNA double-strand breaks in cancer cells as a function of proton linear energy transfer and its variation in time. International Journal of Radiation Biology, 2021, 97(9), 1229-1240, DOI: 10.1080/09553002.2021.1948140, https://doi.org/10.1080/09553002.2021.1948140
    6. Giada Petringa, Marco Calvaruso, Valeria Conte, Pavel Bláha, Valentina Bravatà, Francesco Paolo Cammarata, Giacomo Cuttone, Giusi Irma Forte, Otilija Keta, Lorenzo Manti, Luigi Minafra, Vladana Petkovic, Ivan Petrovic, Selene Richiusa, Aleksandra Ristic Fira, Giorgio Russo and Giuseppe Antonio Pablo Cirrone Radiobiological Outcomes, Microdosimetric Evaluations and Monte Carlo Predictions in Eye Proton Therapy. Applied Sciences, 2021, 11, 8822. https://doi.org/10.3390/app11198822
    7. Wook‐Geun Shin, Dousatsu Sakata, Nathanael Lampe, Oleg Belov, Ngoc Hoang Tran, Ivan Petrovic, Aleksandra Ristic‐Fira, Milos Dordevic, Mario A. Bernal, Marie‐Claude Bordage, Ziad Francis, Ioanna Kyriakou, Yann Perrot, Takashi Sasaki, Carmen Villagrasa, Susanna Guatelli, Vincent Breton, Dimitris Emfietzoglou and Sebastien Incerti. A Geant4‐DNA Evaluation of Radiation‐Induced DNA Damage on a Human Fibroblast. Cancers 2021, 13, 4940. https://doi.org/10.3390/cancers13194940
  • Cooperations:

    Istituto Nazionale di Fisica Nucleare, Laboratori Nazioneli del Sud (INFN-LNS)

    Centre National de la Recherche Scientifique – CNRS, Centre d'Etudes Nucléaires de Bordeaux-Gradignan – CENBG, CNRS/IN2P3/Université Bordeaux

    European Organization for Nuclear Research - Conseil Européen pour la Recherche Nucléaire (CERN)