Baselet Bjorn, Azimzadeh Omid, Erbeldinger Nadine, Bakshi Mayur V, Dettmering Till, Janssen Ann, Ktitareva Svetlana, Lowe Donna J, Michaux Arlette, Quintens Roel, Raj Kenneth, Durante Marco, Fournier Claudia, Benotmane Mohammed A, Baatout Sarah, Sonveaux Pierre, Tapio Soile, Aerts An
Radiobiology Unit, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK•CEN)Mol, Belgium.
Pole of Pharmacology and Therapeutics, Institut de Recherche Expérimentale et Clinique, Université catholique de LouvainBrussels, Belgium.
Front Pharmacol. 2017 Sep 22;8:570. doi: 10.3389/fphar.2017.00570. eCollection 2017.
Radiotherapy is an essential tool for cancer treatment. In order to spare normal tissues and to reduce the risk of normal tissue complications, particle therapy is a method of choice. Although a large part of healthy tissues can be spared due to improved depth dose characteristics, little is known about the biological and molecular mechanisms altered after particle irradiation in healthy tissues. Elucidation of these effects is also required in the context of long term space flights, as particle radiation is the main contributor to the radiation effects observed in space. Endothelial cells (EC), forming the inner layer of all vascular structures, are especially sensitive to irradiation and, if damaged, contribute to radiation-induced cardiovascular disease. Transcriptomics, proteomics and cytokine analyses were used to compare the response of ECs irradiated or not with a single 2 Gy dose of X-rays or Fe ions measured one and 7 days post-irradiation. To support the observed inflammatory effects, monocyte adhesion on ECs was also assessed. Experimental data indicate time- and radiation quality-dependent changes of the EC response to irradiation. The irradiation impact was more pronounced and longer lasting for Fe ions than for X-rays. Both radiation qualities decreased the expression of genes involved in cell-cell adhesion and enhanced the expression of proteins involved in caveolar mediated endocytosis signaling. Endothelial inflammation and adhesiveness were increased with X-rays, but decreased after Fe ion exposure. Fe ions induce pro-atherosclerotic processes in ECs that are different in nature and kinetics than those induced by X-rays, highlighting radiation quality-dependent differences which can be linked to the induction and progression of cardiovascular diseases (CVD). Our findings give a better understanding of the underlying processes triggered by particle irradiation in ECs, a crucial aspect for the development of protective measures for cancer patients undergoing particle therapy and for astronauts in space.
放射治疗是癌症治疗的重要手段。为了保护正常组织并降低正常组织并发症的风险，粒子治疗是一种首选方法。尽管由于深度剂量特性的改善可以使很大一部分健康组织免受辐射，但对于健康组织在粒子照射后发生改变的生物学和分子机制却知之甚少。在长期太空飞行的背景下，也需要阐明这些影响，因为粒子辐射是在太空中观察到的辐射效应的主要促成因素。内皮细胞（EC）构成所有血管结构的内层，对辐射特别敏感，一旦受损，会导致辐射诱发的心血管疾病。转录组学、蛋白质组学和细胞因子分析被用于比较接受或未接受单次2 Gy剂量X射线或铁离子照射的内皮细胞在照射后1天和7天的反应。为了支持观察到的炎症效应，还评估了单核细胞在内皮细胞上的黏附情况。实验数据表明内皮细胞对辐射的反应存在时间和辐射质量依赖性变化。铁离子的辐射影响比X射线更明显且持续时间更长。两种辐射质量都降低了参与细胞间黏附的基因的表达，并增强了参与小窝介导的内吞信号传导的蛋白质的表达。X射线照射后内皮炎症和黏附性增加，但铁离子照射后则降低。铁离子在内皮细胞中诱导的动脉粥样硬化过程在性质和动力学上与X射线诱导的不同，突出了辐射质量依赖性差异，这可能与心血管疾病（CVD）的诱导和进展有关。我们的研究结果有助于更好地理解粒子照射在内皮细胞中引发的潜在过程，这对于为接受粒子治疗的癌症患者和太空中的宇航员制定保护措施至关重要。
