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Cellular response to charged particle irradiation

The objective of this research is to understand the cellular and molecular mechanisms involved in the response of biological systems to ionizing radiations and thus to resolve uncertainties in the risk from environmental exposures to radiation at low and protracted doses. In this interdisciplinary framework, physicists and biologists are conducting a research program based on i) advances in modern molecular biology to investigate damage at the individual cell scale, ii) new instrumentation in ion beam techniques to perform the irradiation of single cells with a counted number of MeV ions, iii) Monte-Carlo simulation for an accurate micro dosimetry at the cellular level.

The charged particle micro beam : view of the irradiation stage and of the ion beam optics. The beam is focused by a quadruplet of magnetic quadrupoles (visible in the foreground). A high resolution CCD camera and an epifluorescence microscope are used to localize each cell automatically [2].

At dose levels typically encountered in private and professional environments, a lot of information is still missing about the molecular pathways and cellular mechanisms that lead from initial deposition of energy to strand breaks and other lesions in DNA. The aim is to develop numerical models of track structure caused by the passage of ionizing particles through living matter and more especially cells and to compare predictions with experimental data. The strategy is not to create another standalone Monte Carlo simulation code, but is rather to integrate the actual knowledge basis of radiobiology into Geant4, a Monte Carlo simulation tool kit developed at CERN and widely used by a large community. Furthermore the efforts of the group are concentrated on understanding the primary molecular processes responsible for recognizing and repairing DNA damage, as well as apoptosis induction at different levels of biological organization from genes or proteins to cells. A charged particle micro beam has been installed for the targeted irradiation of individual cultured cells with a lateral resolution of a few microns. The system is capable of delivering an exact number of ions in cell compartments (cytoplasm or nucleus) in order to control the dose accurately. The development of such an instrument was stimulated by the requirement to avoid any randomness in the dose delivered to each cell of a population, inherent to usual irradiation techniques based on broad beams or radioactive sources. Charged particle micro beams allow the investigation of cell compartment radio sensitivity. The possibility of choosing the target of interest within a cell population or within an individual cell is also of primary importance to understand the role of intercellular and intracellular communication in the response of cells to a low radiation dose.

References :

[1] Ph. Moretto et al., Int. Conf. Microprobe Techniques and Applications, Singapore (2006)
[2] Ph. Barberet et al., Rev. Sci. Inst. 76 (2005) 015101


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