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Distinct vascular genomic effects of proton and gamma radiation

ABSTRACT: We performed comparative RNA sequencing of the early (4 hrs) dose response (0.5 – 200 cGy whole body dose, 10 dose levels) of the mouse aorta to proton and gamma radiation. Total-body proton radiation of conscious animals was performed using a proton beam produced by a cyclotron system, while total-body gamma radiation of animals was performed using a Caesium-137 gamma source. A trend analysis identified genes that showed a dose response, using data permutation to estimate a false discovery rate (q-value) for each gene. We identified 29 and 194 genes (q-value ≤ 0.1) that were upregulated with increasing doses of proton and gamma radiation, respectively. No genes were down-regulated. While fewer genes were dose-responsive to proton radiation, the magnitude of the effect was greater than with gamma radiation. These highly responsive genes were enriched for pathways involved in the response to DNA damage, apoptosis, cellular stress and inflammation (p < 0.01). Gamma radiation responsive genes included the same pathways, but extended to genes in vasculature specific pathways. Genes responsive to both radiation types (19 genes at q-value ≤ 0.1) showed almost perfectly superimposable dose-response relationships. We observed the same superimposable dose response relationship of gamma and proton radiations in a subset of genes validated by quantitative PCR not only in the aorta but also in liver, lung, heart and kidney. Despite a relative similar relative biological effectiveness of protons and gamma photons and the activation of canonical radiation response pathways by both radiation types, we detected marked differences in the genomic response. It seems plausible that these genomic differences translate into differences in the biological processes leading to cardiovascular pathologies.

ORGANISM(S): Mus musculus

PROVIDER: GSE105266 | GEO | 2019/01/25

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.

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Distinct vascular genomic effects of proton and gamma radiation

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