Cancer is the leading cause of death in industrialized countries. At present, the proposed treatments are surgery, chemotherapy, radiotherapy or a combination of these. Conventional radiotherapy uses photons, like X- or gamma-rays, whose dose distribution does not permit to completely spare upstream and downstream healthy tissues. During the past decade, new treatment modalities have emerged: protontherapy and hadrontherapy. However, the studies performed about the potential benefits of such treatments emphasize that more fundamental data is needed to understand the cell response pathways following charged particle irradiation. In this work, a Monte Carlo code (Monte Carlo Survival Curve (MCSC)) was developed to predict the survival fraction of in vitro cells exposed to medium and high LET charged particles. Two cell types were studied: A549 lung cancer cells and EAHy926 endothelial cells. The cell response was assessed following exposure to a broad beam of protons or alpha particles generated by the irradiation facility available at the LARN laboratory. A variety of assays were performed (clonogenic survival, p-H2AX intensity quantification over time, DNA content assessment, lindane exposure) at low, medium and high doses. Taking advantage of the gathered results, MSCS provides the survival fraction of cells in a large dose range and includes two important low dose effects: low dose hypersensitivity and bystander effect. This code simulates the irradiation of a cell population by a broad beam of charged particles and distributes DNA lesions through this population. Lesions are repaired following a reciprocal time model and this repair is stopped at a time which is radiation and cell type dependent. Simulation results are benchmarked to our experimental data and good agreement between both is observed. Importantly, the low dose behaviour is well reproduced. This MCSC code can also prove useful in the response assessment of non-adherent cell lines, as well as in the determination of individual radiosensitivity. The experiments carried out on the A549 cell line after 100 keV/µm alpha particle irradiations have highlighted a strong bystander component at low doses. Although this is an advantage in term of tumor cell killing, this could be detrimental for healthy tissues in which the dose is kept very low. Hence, in vivo studies are needed to assess the bystander effect extent in living organisms.
|la date de réponse
|30 sept. 2013
|Stephane Lucas (Promoteur), Carine Michiels (Copromoteur), Laurent Houssiau (Jury), Sarah Baatout (Jury), Olivier Féron (Jury) & Sylvain Costes (Jury)