Comparative gene expression analysis after exposure to 123I-iododeoxyuridine, γ- and α-irradiation. Comparative gene expression analysis after exposure to 123I-iododeoxyuridine, γ- and α-irradiation

Gene expression analysis was carried out in human T-lymphoma Jurkat cells in order to identify candidate genes showing significant gene expression alterations allowing robust discrimination of the Auger emitter 123I, incorporated into the DNA as 123I-iododeoxyuridine (123IUdR), compared to α- and γ-radiation, which may be useful for biodosimetry purposes. Comparative gene expression analysis was performed employing whole human genome DNA microarrays. The gene expression of all candidate genes was validated by quantitative real-time PCR. 155, 316 and 982 genes were exclusively regulated after exposure to 123IUdR, α-particles and γ-rays, at equi-effect doses/activity, respectively. Applying the stringent requirements for candidate genes, four , one and one gene(s) were identified allowing a reliable discrimination between γ- versus 123IUdR exposure, γ- versus α-radiation and α- versus 123IUdR exposure, respectively. Gene expression analysis might be an effective tool for the general discrimination of radiation qualities and might help to elucidate different biological effectiveness on the mechanistic level. Overall design: The formation of γ-H2AX foci after exposure to different radiation qualities was analyzed to determine equi-effect doses/activities and consequently to compare gene expression on a similar DNA damage effect level. A similar DNA damage effect level was found after exposure to 10 Gy γ-rays, 1 Gy α-particles and after 20 h exposure to 123IUdR, which corresponded roughly to 2600 accumulated 123I decays per cell. Genes with a fold-change > 1.5 and a FDR 1.5 fold after exposure to a specific radiation quality and display no altered (1-fold ± 0.1) or even opposing (>1.1-fold) regulation in response to the other radiation qualities. Concomitantly, we used P values, which were not adjusted using the FDR, for the analysis of the significance in order to consider more genes. However, this loss of statistical stringency was justified because the gene expression level of the candidate genes were verified and validated by quantitative real-time PCR .