Gene expression analysis after exposure to I-123-iododeoxyuridine, γ-rays and α-particles
Gene expression analysis after exposure to I-123-iododeoxyuridine, γ-rays and α-particles
Gene expression analysis was carried out in human p53-deficient T-lymphoma Jurkat cells in order to identify robust candidate genes showing significant gene expression alterations allowing the discrimination of radiation qualities.Equi-effect radiation doses, i.e. radiation doses and exposure condit...
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Personal Name(s): | Unverricht, Marcus (Corresponding Author) |
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Giesen / Pomplun, Ekkehard / Kriehuber, Ralf | |
Contributing Institute: |
Sicherheit und Strahlenschutz, Umgebungsüberwachung,Strahlenbiologie; S-US |
Published in: | 2014 |
Imprint: |
2014
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Conference: | 41th Annual Meeting of the European Radiation Research Society, Rhodes (Greece), 2014-09-14 - 2014-09-19 |
Document Type: |
Conference Presentation |
Research Program: |
ohne Topic |
Subject (ZB): | |
Link: |
OpenAccess OpenAccess |
Publikationsportal JuSER |
Gene expression analysis was carried out in human p53-deficient T-lymphoma Jurkat cells in order to identify robust candidate genes showing significant gene expression alterations allowing the discrimination of radiation qualities.Equi-effect radiation doses, i.e. radiation doses and exposure conditions causing the same biological effect level, were determined with regard to micronucleus formation, γ-H2AX foci signal intensity and apoptosis induction after γ-irradiation (Cs-137; dose range: 0.8-10 Gy), α-particle exposure (Am-241; dose range: 0.1-1 Gy) and exposure to the Auger electron emitter I-123 as I-123-iododeoxyuridine (I-123-UdR; activity range: 4-200 kBq per 10E6 cells). I-123-UdR was incorporated into the DNA for 20 h. Absorbed radiation dose was assessed based on accumulated decays, point-kernel calculations and the 3-D morphology of the cells. Gene expression analysis was performed employing whole human genome DNA-microarrays (Agilent) after exposure to equi-effect radiation doses of all three investigated radiation qualities. RNA for gene expression analysis was isolated 6 and 24 h post-exposure. Only genes showing a >1.5-fold change of expression vs. non-irradiated control were further analyzed for significance. Potential candidate genes for the discrimination of radiation quality have to show (i) a significant expression change after exposure to a specific radiation quality and (ii) display no altered gene regulation (1-fold ± 0.1) or even a conversely (>1.1-fold) regulation in response to exposure to the other radiation qualities investigated. Gene expression of all selected candidate genes was validated via qRT-PCR. Biological processes and pathways of significantly regulated genes were subsequently analyzed. At equi-effect doses the results of the gene expression analysis showed that 359, 598 and 1339 genes are significantly regulated after exposure to I-123-UdR, α-particles and γ-rays, respectively. Applying our stringent requirements for candidate genes, we identified only 4, 1 and 1 gene(s) allowing the reliable and robust discrimination between γ- vs. I-123-UdR-exposition, γ- vs. α-radiation and α- vs. I-123-UdR-exposition, respectively. γ-rays induce pronounced alterations in gene expression in Jurkat cells when compared to I-123-UdR and α-particles at equi-effect radiation doses. In vitro gene expression analysis in Jurkat cells might suggest that the discrimination of different radiation qualities by means of gene expression is possible.Funded by Bundesministerium für Bildung und Forschung (BMBF), Project No.: 02NUK005A |