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Low- and middle-dose of radiation on hNPC and HUVEC

ABSTRACT: Many neural progenitor cells present in the fetus, but also in adult brain, which play a major role for the reproduction for healingin regeneration of neuronal cells, when differentiated cells are damaged. However, effects of radiation effect on undifferentiated neural progenitor cells remained unclear. The radiation doses of medical exposure, pollution by nuclear power plant accidents, and other exposure of workers; medical workers, airline crews, and astronaut have been focused. In this study, we report the effects of low- to middle- dose doses of radiation on cultured human neural progenitor cells (hNPC) differentiated derived from embryonic stem (ES) cells, which are partially compared with those of human umbilical vein endothelial cell (HUVEC). Gene expression was changed by continuous exposure of 31mGy; 0.0072 mGy/ minute, 124mGy; 0.029 mGy/ minute and 496mGy; 0.085 mGy/ minute for seventy-two hours. While shortening in neurite length by 124mGy was not significant, its decrease was observed by 496 mGy of radiation. Number of altered pathways increased dose-dependently. By thirty-one mGy per 72 hours of radiation, gene expression of inflammatory pathways involving interferon and cell junction were changed. By 124 mGy of radiation, DNA double strand break repair pathways and cell adhesion molecules were affected. Then, 496 mGy of radiation for 72 hours altered translational DNA synthesis pathway, apoptotic pathway, various metabolic pathways and neural differentiation pathways. Dose-dependent transcriptional changes by low- to middle- radiation are consistent with gradual axonal shortening, growth arrest and neural cell death.

ORGANISM(S): Homo sapiens

PROVIDER: GSE67309 | GEO | 2015/03/31

SECONDARY ACCESSION(S): PRJNA279481

REPOSITORIES: GEO

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Project description:In the current study a systematic investigation of life stage, tissue and cell dependent sensitivity to ionizing radiation in the nematode Caenorhabditis elegans was conducted. This revealed that individuals that have reached the post-mitotic L4 stage showed no significant effects with respect to mortality, morbidity or reproduction when subjected to either acute dose ≤6 Gy(1500 mGy/h) or chronic exposure ≤4 Gy( ≤ 100 mGy/h). In contrast, chronic exposure from embryo to young adult stage caused a dose and dose rate dependent reprotoxicitiy with 43% reduction in total brood size at 6.7Gy (107 mGy/h). Systematic targeted irradiation of developmental stages showed that exposure during L1 to young L4 was sufficient to induce reprotoxic effects. Exposure during these stages was associated with a dose rate dependent genotoxic effects on gonads with 1.7 to 3.2 fold increase in germ cell apoptosis in larvae subjected to 40-100 mGy/h, respectively. Importantly, exposure to gamma radiation significantly impaired spermatogenesis in a dose rate dependent manner. The observed reduction in the number of spermatids accounted for xx% of the reprotoxic effects, thus signifying spermatids as the most radiosensitive cell type in C. elegans. Molecular responses analyzed by RNAseq of nematodes irradiated from L1 to L4 stage revealed a significant enrichment of genes related to both male and hermaphrodite reproductive processes. Gene network analysis identified adverse genotoxic effects related to down-regulation of genes required for spindle formation and sperm meiosis/maturation, including smz-1, smz-2 and htas-1. The expression of a subset of 28 set-17 regulated Major Sperm Proteins (MSP) required for spermatids production was correlated to the reduction in reproduction and the number of spermatids, thus corroborating the impairment of spermatogenesis as the major cause of gamma radiation induced life-stage dependent reprotoxic effect. Furthermore, the progeny of irradiated nematodes showed significant embryonal DNA damage that was associated with persistent effect on somatic growth. Unexpectedly, these nematodes did however maintain much of their reproductive capacity in spite of the reduced growth.

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Low- and middle-dose of radiation on hNPC and HUVEC

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