Genotoxicity of Iodine-123 labeled 5-Iodo-2´-deoxyuridine in comparison to high- and low-LET radiation
Genotoxicity of Iodine-123 labeled 5-Iodo-2´-deoxyuridine in comparison to high- and low-LET radiation
To determine the genotoxic effects after exposure to Iodine-123 labeled 5-Iodo-2´-deoxyuridine (I-123-UdR) in comparison to α- and γ-irradiation, micronucleus (MN) induction and γ-H2AX formation were analyzed.Jurkat cells were either exposed to I-123-UdR for 20 h or irradiated with different doses o...
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Personal Name(s): | Unverricht, Marcus (Corresponding author) |
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Giesen, Ulrich / Pomplun, Ekkehard / Kriehuber, Ralf | |
Contributing Institute: |
Sicherheit und Strahlenschutz, Umgebungsüberwachung,Strahlenbiologie; S-US |
Imprint: |
2015
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Conference: | 8th International Symposium on Physical, Molecular, Cellular and Medical Aspects of Auger Processes, Nara (Japan), 2015-05-20 - 2015-05-22 |
Document Type: |
Poster |
Research Program: |
ohne Topic |
Subject (ZB): | |
Link: |
OpenAccess OpenAccess |
Publikationsportal JuSER |
To determine the genotoxic effects after exposure to Iodine-123 labeled 5-Iodo-2´-deoxyuridine (I-123-UdR) in comparison to α- and γ-irradiation, micronucleus (MN) induction and γ-H2AX formation were analyzed.Jurkat cells were either exposed to I-123-UdR for 20 h or irradiated with different doses of γ-rays (Cs-137, 0.7 Gy/min) or α-particles (Am-241, 0.032 Gy/min). Cells were assayed for MN formation employing automated image analysis (MetaSystems, Germany). The γ-H2AX foci, as a measure of DNA double-strand-breaks (dsb), were quantified by measuring the mean overall signal intensity of foci per cell using flow cytometry and by counting the number of individual foci with a fluorescence microscope.γ-H2AX foci number per cell showed a much more pronounced increase after exposure to I-123-UdR per dose unit when compared to γ- and α-irradiation. However, the mean intensity of total foci signal per cell, as measured by flow cytometry, was very similar for exposure to I-123-UdR and α-particles. Single γ-H2AX foci induced by I-123-UdR appeared to be smaller and/or less intense stained than those after α-irradiation and resembled foci induced by γ-rays. The distribution of the cellular γ-H2AX fluorescence signals showed that the dose distribution of single cells was more heterogenous after exposure to I-123-UdR and α-particles when compared to γ-irradiation. MN induction was almost identical for all three investigated radiation qualities.γ-H2AX foci are very efficiently induced by I-123-UdR per unit dose when compared to γ- and α-radiation, probably because almost every I-123 decay occurred within the DNA. The presumed complexity of DNA-lesions caused by DNA-associated AEE is neither reflected in size nor intensity of individual foci. The microscopic quantification of γ-H2AX foci indicates that I-123 induced dsb are less prone to be transferred into an MN. The MN induction after exposure to I-123-UdR and α-particles could be underestimated because highly damaged cells within the heterogenous exposed cell population are not adequately represented in the MN assay. As α-particle-induced foci are aligned along the track, individual foci are hard to count, we suggest that flow cytometry is a more appropriate analysis tool to quantify LET-dependent γ-H2AX foci induction. Funded by Bundesministerium für Bildung und Forschung (BMBF), Grant No.: 02NUK005A |