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Cardiovascular risk after radiation exposure.
Vortrag: Gesellschaft für Biologische Strahlenforschung Tagung, 2nd October 2009, Essen, Germany. (2009)
It is well established that high doses of ionising radiation, such as used in radiotherapy, increase risk of cardiovascular diseases (CVD). In contrast, there are considerable uncertainties concerning health effects of low doses of ionising radiation on heart. The most convincing data showing excess radiation-associated risk for CVD has been observed in the Life Span Study of the Japanese atomic bomb survivors. Importantly, even at doses as low as 0.5 Gy the mortality and morbidity due to hypertension and myocardial infarction were increased.
Whether the biological responses in the case of high and low doses of ionising radiation are similar is still largely unknown. However, in contrast to high-dose radiation, acute doses in the range 0.1–1 Gy result in down-regulation of the adhesion of leukocytes to the endothelium both in vitro and in vivo and thus may have an anti-inflammatory effect. Furthermore, it is reasonable to believe that not only the dose but also the dose rate has an effect on the biological outcome.
We have used both a human endothelial cell line and a mouse model to study the immediate proteomic effects of in vitro irradiation and long-term functional effects of heart-focussed in vivo irradiation, respectively.
The human endothelial cell line Ea.hy926 was irradiated with 0.2 Gy Co-60 gamma rays with two different dose rates (20 mGy/min and 200 mGy/min) and the cells were harvested 4h and 24 h after the irradiation. The proteome changes in the sham-irradiated vs. irradiated cytosolic fractions were analysed using 2 DE-DIGE techniques. Out of more than fifty protein spots that showed significant alterations in their expression 22 proteins were identified. Among the pathways affected by the low-dose ionising radiation are Ran and Rho/Rock pathways, stress response and glycolysis.
Functional and proteomic alterations in mitochondria isolated from irradiated and sham-irradiated murine (C57Bl6) hearts 4 weeks after heart-focussed irradiation (0.2 Gy, 2 Gy X ray) were analysed. No differences between sham- and irradiated cardiac mitochondria were found in swelling, respiratory coupling and production of ATP. However, we could identify significantly increased ROS formation in cardiac mitochondria 4 weeks after the exposure to 2 Gy ionising radiation.
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Publikationstyp
Sonstiges: Vortrag
Konferenztitel
Gesellschaft für Biologische Strahlenforschung Tagung
Konferzenzdatum
2nd October 2009
Konferenzort
Essen, Germany
Institut(e)
Institute of Radiation Biology (ISB)