Poster (After Call) FZJ-2017-08370

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Genotoxicity of Iodine-123 labeled 5-Iodo-2´-deoxyuridine in comparison to high- and low-LET radiation

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2015

8th International Symposium on Physical, Molecular, Cellular and Medical Aspects of Auger Processes, NaraNara, Japan, 20 May 2015 - 22 May 20152015-05-202015-05-22

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Abstract: 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

Keyword(s): Biology (2nd)


Contributing Institute(s):
  1. Sicherheit und Strahlenschutz, Umgebungsüberwachung,Strahlenbiologie (S-US)
Research Program(s):
  1. 899 - ohne Topic (POF3-899) (POF3-899)

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 Record created 2017-12-13, last modified 2021-01-29