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Long terms effects of very low dose particle radiation on the gene expression in the mouse heart

ABSTRACT: We sought to determine the long-term effects of radiation (IR) on gene expression in the whole heart as a function of IR type and dose. We hypothesize that compared to low doses of gamma-IR, high charge and energy (HZE) particle-IR may have different biological response thresholds in cardiac tissue at lower doses, and these effects may be IR type- and dose-dependent. We provide for the first time the transcriptome analysis of mouse hearts exposed to low and very low doses of gamma- (137Cs), silicon- (14Si), and titanium- (22Ti) irradiation. Our results show that 16 months after low and very low dose IR exposure, the gene expression in the heart tissue is significantly differentially regulated, suggesting there are long-term effects on dysregulation of varying molecular pathways that are associ-ated with various degrees of cardiovascular, pulmonary and metabolic diseases, as well as biological processes, including abnormal circadian rhythm, cancer, Hutchinson-Gilford progeria syndrome, etc.

ORGANISM(S): Mus musculus

PROVIDER: GSE164234 | GEO | 2021/01/05

REPOSITORIES: GEO

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Project description:Following nuclear accidents and the increasing use of radionuclides, environmental radiation radiological protection is a source of major concern, particularly in the context of low doses. Ionizing radiation (IR) may lead to genetic mutations, chromosomal rearrangements and epigenetic modifications. The present study focuses on the in vivo effects of low to moderate doses of IR on zebrafish early embryonic development. The effects of IR on the transcriptome were studied at the shield stage (6 hours post-fertilization, hpf) and at dose rates from 50 mGy/h to 0.005 mGy/h. The effects on the methylome by whole genome bisulfite sequencing were investigated at the same stage and at dose rates of 50 mGy/h and 5 mGy/h.IR exposure impacted the expression of genes involved in germ layers specification during gastrulation of zebrafish embryos. Moreover, changes in mitochondrial energetic metabolism were detected at all dose rates. Different transcriptomic responses were observed between groups irradiated at the two highest dose rates, 50 mGy/h and 5 mGy/h and those irradiated at the three lower dose rates. However, the transcriptomic analysis revealed an impact of IR on development, neurogenesis and muscular development at 50 mGy/h, 5 mGy/h and 0.5 mGy/h. The global level of methylation was not changed after exposure to IR, and no widespread changes in transposable elements were detected. Rather, we observed that IR induced loci specific demethylation in the promoter of genes involved in development, neurogenesis and myogenesis. Interestingly, this promoter hypomethylation was equally associated with a change in gene expression. In this study, both DMR and gene expression analysis pointed toward a specific deregulation of genes involved in development, neurogenesis and myogenesis. The modification of the methylation pattern in promoters of genes involved in central nervous system development and muscle development seems to be responsible of transcriptomic changes. This study confirms previous results obtained at later developmental stages, showing that neurogenesis and muscle development were also impacted at 50 mGy/h, 5 mGy/h and 0.5 mGy/h with phenotypic alterations in terms of muscle histology and swimming behaviour. This suggests that early developmental perturbations are predictive of functional defects at later developmental stages.

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Long terms effects of very low dose particle radiation on the gene expression in the mouse heart

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