Abstract
Background: High-LET ion irradiation is being more and more often used to control tumors in patients. Given that tumors are now considered as complex organs composed of multiple cell types that can influence radiosensitivity, we investigated the effects of proton and alpha particle irradiation on the possible radioprotective cross-talk between cancer and endothelial cells. Materials and Methods: We designed new irradiation chambers that allow co-culture study of cells irradiated with a particle beam. A549 lung carcinoma cells and endothelial cells (EC) were exposed to 1.5 Gy of proton beam or 1 and 2 Gy of alpha particles. Cell responses were studied by clonogenic assays and cell cycle was analyzed by flow cytometry. Gene expression studies were performed using Taqman low density array and by RT-qPCR. Results: A549 cells and EC displayed similar survival fraction and they had similar cell cycle distribution when irradiated alone or in co-culture. Both types of irradiation induced the overexpression of genes involved in cell growth, inflammation and angiogenesis. Conclusions: We set up new irradiation chamber in which two cell types were irradiated together with a particle beam. We could not show that tumor cells and endothelial cells were able to protect each other from particle irradiation. Gene expression changes were observed after particle irradiation that could suggest a possible radioprotective inter-cellular communication between the two cell types but further investigations are needed to confirm these results.
Highlights
Radiotherapy plays an important role in cancer treatment since more than 50% of all cancer patients will receive at least one session of radiation therapy during their treatment [1]
Given that we observed an accumulation of both cell types in G2/M phase, we investigated the gene expression of p21, a well-known protein involved in cell cycle arrest
We developed new irradiation chambers allowing indirect co-culture study in order to investigate the effect of alpha particle irradiation on a lung tumor cell line and endothelial cells in terms of cell survival, cell cycle arrest and gene expression changes
Summary
Radiotherapy plays an important role in cancer treatment since more than 50% of all cancer patients will receive at least one session of radiation therapy during their treatment [1]. The use of charged particles in radiotherapy has several advantages over X-rays, the most important of which is the more precise dose distribution within the target volume For this reason, charged particles are already used to treat paediatric patients and tumors located near critical healthy tissues, such as melanoma of the eye, chordomas and chondrosarcomas at the base of the skull [3]. Because of their high linear energy transfer (LET), heavy charged particles, such as carbon or helium ions, produce an intense ionization along their track and cause severe DNA damage which is more difficult to repair than that caused by sparsely ionizing radiation like X-rays [4].
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