Coppes, R. P.

Dettmering, T.

Durante, M.

Faber, H.

Fournier, C.

Ghobadi, G.

Simoniello, P.

van Luijk, P.

Zink, J.

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Carbon ion induced vascular damage in the rat lung∗J. Zink1, T. Dettmering†1, H. Faber2, G. Ghobadi2, P. Simoniello1, M. Durante1, P. van Luijk2,R. P. Coppes2, and C. Fournier11GSI, Darmstadt, Germany; 2Departments of Cell Biology and Radiation Oncology, University Medical CenterGroningen, University of Groningen, The NetherlandsIntroductionBronchial carcinomas are one of the most frequentcauses of death in Germany. Radiotherapy is used in pro-gressed stages of the cancer if the tumor cannot be removedsurgically. The aim of radiotherapy is to control tumorgrowth by the administration of a high dose while the nor-mal tissue surrounding the tumor is intended to be spared.Charged particles have the beneficial feature of an inversedepth dose distribution which means that the normal tis-sue can be spared while a high dose is absorbed by the tu-mor [1]. However, doses to the healthy tissue may be highenough to provoke side effects like pneumonitis or fibrosis.These effects are preceded by vascular damage, which isconsidered to be related to the pathogenesis of pneumonitisand fibrosis [2]. Here we investigated the impact of Carbonions on blood vessel damage in the rat lung.Materials and MethodsLungs of adult male albino Wistar rats were irradiatedwith 270 MeV/u Carbon ions. Either 100% of lungs wereirradiated (8.5 Gy or 12.5 Gy) or 50% (17.25 Gy) as de-scribed in [3]. After 8 weeks animals were sacrificed andlungs embedded in paraffin. Lung slices were stained withVerhoeff-van-Gieson staining, which allows distinguishingthe different layers of a blood vessel. Vessel occlusion wasdetermined by calculating the ratio of the thickness of theTunica media to the diameter of the Membrana elastica ex-terna. Only vessels with a maximum diameter of 50 µmand round shape were considered. Analysed vessels of 50%irradiated lungs were located exclusively in irradiated areasof the lungs.Results and DiscussionA thickening of the vessel wall, mainly of the Tunicamedia, was observed after irradiation, which led to an oc-clusion of the blood vessel (Fig. 1). A higher dose induceda more pronounced occlusion of the blood vessels in com-parison to a lower dose of Carbon ions (Fig. 2A). Inter-estingly, a higher irradiation volume had, despite the lowerlocal dose, a stronger effect on the induced vessel occlusionthan a smaller irradiation volume (Fig. 2B).These results show for Carbon ions similar effects al-ready reported for protons to blood vessels in the lung [4],∗Supported by HGS-HIRe and grant CBR-754842 from the Universityof Groningen† t.dettmering@gsi.dewhich show that a low dose administered to a large volumeis more efficient than a high dose to a small volume. Thethickening of the vessel wall is probably due to an increasedproliferation of smooth-muscle cells (SMC) that form theTunica media, but potentially also due to an invasion ofSMC into the Tunica intima. It was already shown that ir-radiated endothelial cells enhance the proliferation of SMC[5].Figure 1: Representative example of a normal blood ves-sel (A) in comparison to an irradiated vessel 8 weeks afterirradiation with Carbon ions (B).Figure 2: Vessel occlusion in the rat lung 8 weeks after ir-radiation with Carbon ions. Either the whole lung was irra-diated (8.5 Gy and 12.5 Gy) or only 50% of the lung. PanelA shows the dose effect and panel B the volume effect.References[1] Kraft, G. (2000). Progr in Particle and Nuclear Phys.[2] Coggle, J.E. et al. (1986). Environ Health Perspect.[3] Coppes, R.P. et al. (2011). Int J Radiat Oncol Biol Phys.[4] Ghobadi, G. et al. (2011). Thorax.[5] Milliat et al. (2006). Am J Pathol.GSI SCIENTIFIC REPORT 2013 BIOPHYSICS-21doi:10.15120/GR-2014-1-BIOPHYSICS-21 223

Carbon ion induced vascular damage in the rat lung

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Carbon ion induced vascular damage in the rat lung

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