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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE104222 | GEO | 2020/09/01

REPOSITORIES: GEO

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Project description:In the summer of 2012, one year after the 3.11 accident at Fukushima Daiichi nuclear power plant following the Great Tohoku Earthquake, a project was initiated to examine the effects of low-level gamma radiation on rice plants. The site of the experiment was the highly contaminated Iitate village in Fukushima prefecture of Japan. The basic experimental strategy was to expose healthy rice seedlings to continuous low-dose gamma radiation and examine the morphological and molecular genetic changes therien. Selected gene expression profiles of internal control, DNA replication/repair, oxidative stress, photosynthesis, and defense/stress functions were examined by semi-quantitative RT-PCR. Results revealed that low-level gamma radiation affects the expression of numerous genes, in particular showing the early (6 h) induction in DNA repair/damage-related genes and the late (72 h) induction of a previously described marker gene for defense/stress responses. Based on these results, which confirmed our data from preliminary experiments using detached rice leaves for radiation exposure, we proceeded for DNA microarray analysis. Using the established dye-swap approach, we analyzed the differentially expressed genes at 6 and 72 h time points using a whole rice genome 4 x 44 K custom chip. Obtained results showed that exposure to low-level gamma radiation differentially regulated 4481 (induced) and 3740 (suppressed) and 2291 (induced) and 1474 (suppressed) rice leaf genes at 6 and 72 h post-exposure, respectively, by at least two-fold changes. MapMan bioinformatics tool was also used to produce diagrams of the potential pathways, based on the input gene expression data of highly changed genes, operating downstream of the gamma radiation perception by rice plant.Inventory of a large number of gamma radiation-responsive genes in leaves provide new information and increased knowledge on novel regulatory processes in rice. The highly contaminated Iitate Farm (ITF), which is located 31 Km from the damaged nuclear power plant and having a background radiation level over 100 times (~ 5 microSv/h) than normal, was the designated place for the re-examination of low-level gamma radiation experiments using rice as a model system. As our group had a decade of experience and data on the effects of gamma radiation on leaf segments, the experimental was designed in such a way so as to expose whole rice plants to gamma radiation being emitted from the contaminated ground and examine the morphological and molecular genetic changes in the leaves under a dose-dependent manner.

Project description:Alpha (α)-radiation is a ubiquitous environmental agent with epigenotoxic effects. Human exposure to α-radiation at potentially harmful levels can occur repetitively over the long term via inhalation of naturally occurring radon gas that accumulates in enclosed spaces, or as a result of a single exposure from a nuclear accident. Alterations in epigenetic DNA methylation (DNAm) have been implicated in normal aging and cancer pathogenesis. Nevertheless, the effects of aberrations in the methylome of human lung cells following exposure to single or multiple α-radiation events on these processes remain unexplored. Here, we performed genome-wide DNAm profiling of human embryonic lung fibroblasts from control and irradiated cells using americium-241 α-sources. Cells were α-irradiated in quadruplicates to seven doses using two exposure regimens, a single-fraction (SF) where the total dose was given at once, and a multi-fraction (MF) method, where the total dose was equally distributed over 14 consecutive days. Our results revealed that SF irradiations were prone to a decrease in methylation levels, while MF irradiations mostly increased methylation. The analysis also showed that the gene body (i.e. exons and introns) was the region mostly altered by both the SF hypomethylation and the MF hypermethylation. Additionally, the MF irradiations induced the highest number of differentially methylated regions in genes associated with DNAm biomarkers of aging, carcinogenesis, and cardiovascular disease. The DNAm profile of the oncogenes and tumour suppressor genes suggested that the fibroblasts elicited a defensive response to the MF α-irradiation. Key DNAm events of ionizing radiation exposure including changes in methyl levels in mitochondria dysfunction-related genes were mainly identified in the MF groups. However, these alterations were under-represented, indicating that the mitochondria undergo adaptive mechanisms, aside from methylation, in response to radiation-induced oxidative stress. In this study, we identified a contrasting methylomic profile in the lung fibroblasts α-irradiated to SF compared with MF exposures. These findings demonstrate that the methylome response of the lung cells to α-radiation is highly dependent on both the total dose and the exposure regimen. They also provide novel insights into potential biomarkers of α-radiation which may lead to the development of innovative approaches to detect, prevent and treat α-particle related diseases.

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

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