Abstract
Background and Purpose: 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.Materials and Methods: 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.Results: 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.Conclusions: 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.
Highlights
The main goal of radiotherapy is to efficiently target and eradicate tumors while sparing surrounding healthy tissues (Bentzen, 2006; Barnett et al, 2009)
Due to the limited number of patients treated with particle therapy at present, induction of normal tissue damage cannot be predicted correctly as molecular pathways and biological functions altered by high linear energy transfer (LET) radiotherapy are still largely unknown (Schulz-Ertner and Tsujii, 2007; Durante and Loeffler, 2010; Newhauser and Durante, 2011)
Little is known about the effects of high LET irradiation in the context of radiation-induced cardiovascular diseases (CVD)
Summary
The main goal of radiotherapy is to efficiently target and eradicate tumors while sparing surrounding healthy tissues (Bentzen, 2006; Barnett et al, 2009). One of the recent developments in radiotherapy modalities is high linear energy transfer (LET) particle therapy (Stone et al, 2003) In this technique, accelerated charged particle beams, such as proton and carbon ions, are used (Wilson, 1946), which have improved depth dose characteristics in comparison to low LET radiotherapy (Durante and Loeffler, 2010). Tumors can be irradiated with great precision, minimizing the dose to surrounding healthy tissues Besides their physical advantage, charged particle beams induce more damage per unit of dose, i.e., demonstrate a higher relative biological effectiveness (RBE) compared to conventional low LET X-ray radiotherapy (Kramer et al, 2003; Schulz-Ertner and Tsujii, 2007). 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
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