Frieß, J.

Heselich, A.

Layer, P. G.

Ritter, S.

Thielemann, C.

GSI Repository

Effects of X-rays and titanium ions on cardiomyocyte cultures∗J. Frieß1, A. Heselich2, S. Ritter3, P. G. Layer2, and C. Thielemann11University of Applied Sciences Aschaffenburg, Germany; 2Technische Universita¨t Darmstadt, Germany; 3GSI,Darmstadt, GermanyMotivationFor the pursuit of the planning of manned space mis-sions to Mars [1; 2] as well as for the application of heavyion irradiation in radio-therapy [3] an assessment of pos-sible effects of high LET radiation on the cardiovascularsystem, especially heart muscle cells is needed. In order toapproach this important field, we used for the first time mi-croelectrode arrays (MEA). This method allows the record-ing and monitoring of electrophysiologic cardiac signals ofprimary cardiac cultures, seeded onto MEA-chips. Addi-tionally, DNA damage and cell cycle progression were ex-amined.Material and MethodsCardiac cells were isolated from chicken at develop-mental embryonic stage E8 and cultivated. Cells wereseeded onto 60 electrode MEAs and 15 mm coverslips.The cultures were exposed to carbon (25 mm Bragg Peak,mean LET 75 keV/µm at sample position) or titanium ions(1 GeV/u) at the SIS-facility (GSI, Germany). X-ray ex-posure was conducted at the Technische Universita¨t Darm-stadt (135 kV; 19 mA / 90 kV; 33.7 mA). Electrophysio-logical properties of the cell cultures were measured be-fore and after exposure. Signals of cardiac cells could berecorded for approximately one week and were analysed interms of beat rate, conduction velocity, field action poten-tial duration and general spike shape using the MATLABsoftware tool DrCell [4]. Cardiomyocytes cultured on cov-erslips were fixed at different time points after exposureand double strand break (DSB) accumulation and repair,proliferation and apoptosis were examined by immunohis-tochemistry.ResultsExperiments up to now indicate that heavy ion irradia-tion reduces the conduction velocity of cardiac signals [5].Furthermore, cultures irradiated with titanium ions show aslight increase in the field action potential durations fourhours after exposure compared to the sham irradiated con-trols (see figure 1). In contrast, cultures exposed to thesame doses of X-rays exhibit a reduction in their field ac-tion potential duration in comparison to the non-irradiatedcontrols. These results indicate different radiation qualitiesmay have opposing effects on the electrophysiology of the∗This work is supported by the DLR and ESA in the frame of the ESAIBER-10 program.Figure 1: Field action potential durations (fAPd) are ex-emplarily plotted for cultures exposed to 2 Gy X-ray andtitanium ions, respectively.exposed cells. This is also supported by other physiologicparameters such as the beat rate.For both, X-ray and heavy ion radiation, we observeda late, but dose-dependent G1/S-checkpoint response ana-lyzed by S-phase labeling. Irradiation with higher dosesof heavy ions resulted in a stronger decrease of prolifer-ation compared to similar doses of X-rays. We detectedonly small differences in G2/M-activation. We also ob-served a dose-dependent decrease in the number of mitoticfigures 24 h after X-irradiation, whereas irradiation withheavy ions showed only slight decreasesConclusionX-ray and titanium ion exposure show opposing ef-fects on some electrophysiologic characteristics at the samedoses.References[1] Space Studies Board, National Research Council, “Radia-tion Hazards to Crews of Interplanetary Missions” NationalAcademy Press, Washington DC, 1996[2] R. J. White et al., “Humans in space”, Nature, 2001,409(6823), p. 1115[3] M. P.Little et al., “Review and meta-analysis of epidemiolog-ical associations between low/moderate doses of ionising ra-diation and circulatory disease risks, and their possible mech-anisms.”, Radiat Environ Bio-phys, 2010 49(2), p. 139–53[4] C Nick et al., “DrCell – A Software Tool for the Analysisof Cell Signals recorded with extracellular Microelectrodes”,Signal Processing: An International Journal (SPIJ), 2013-2;7(2), p. 96-109[5] J. Frieß et al, “Electrophysiological Effects of Heavy Ion Ir-radiation on Cardiomyocytes”, GSI Report 2012 (2013) 480GSI SCIENTIFIC REPORT 2013 BIOPHYSICS-17doi:10.15120/GR-2014-1-BIOPHYSICS-17 219

Effects of X-rays and titanium ions on cardiomyocyte cultures

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Effects of X-rays and titanium ions on cardiomyocyte cultures

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