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Haser Sutcu

Salón de actos de Biogipuzkoa

17/09/24

13:30

DNA is the major target of radiation therapy of malignant tumors. Amongst ionizing-radiation (IR)-induced DNA damage, DNA double-strand breaks (DSBs) are one of the most severe DNA lesions a cell can incur, leading to cell death. Despite the day-by-day improvements of cancer diagnosis and treatments, tumor-neighboring healthy tissues are still exposed to IR and subject to late side effects, impacting the life quality of patients. Skeletal muscle, which holds 40% of the body mass, is one of those tissues most likely to be affected.

 

Nowadays, therapies based on the use of charged particles are becoming more and more popular method of radiotherapy, and there are multiple fundamental and clinical studies on going, to improve the treatment and prevent the undesired side effects. Thus, with this aim, and to increase the understanding of the irradiation-induced DNA damage response in muscle cells, we used MIRCOM microbeam facility (Institute of Radioprotection and Nuclear Safety – Cadarache, France) to irradiate defined regions in the cell nucleus with a controlled number of charged protons or alpha particles at a high spatio-temporal resolution. Hence, we studied the DNA DSB repair (DSBR) activity along the myogenic differentiation of myoblasts into myotubes. Here, we demonstrated that: 1) myotubes, post-mitotic myogenic cells, display reduced DNA damage response upon ionizing radiation, and 2) in myoblasts, proliferating myogenic cells, the DSBR mechanisms engaged and the repair dynamic changes depending on the characteristic and type of ionizing particle.