Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression profile of peripheral blood leukocytes of 60Co gamma-ray accidently-irradiated persons

ABSTRACT: In order to identified as candidate biomarkers for early diagonosis or as therapeutic targets in late damages of ionizing radiation, gene expression profile was analyzed in the peripheral blood of three 60Co γ-ray accidently-exposed persons. The results showed that there were 285 up-regulated and 446 down-regulated genes in irradiated samples compared with control samples. The large majority of those differentially expressed genes encode proteins that are associated with immune response, inflammation, cell structure, oxidative stress, neuro-hormone regulation, reproduction, susceptibility of psychiatric disorders, and transcriptional regulators. The expressions of IL3, KDR, CEACAM8 and OSM were validated by real-time RT-PCR method. The findings of our study should help us understanding the molecular mechanisms underlying the late effects of ionizing radiation and to develop better diagonostic and therapeutic strategies for those damages. Fresh blood samples were collected from three 60Coγ-Ray accidentally-exposed persons(3 years post irradiation) and three non-irradiated healthy donors. Leucocytes cells were isolated and total RNA was extracted. Four RNA samples, from three accidently-exposed persons and a RNA mixture extracted from a combination of three healthy donors` leucocytes (ratio 1:1:1, each 3.3×106 cells) in EL buffer, were subjected to Agilent gene expression microarray assay.

ORGANISM(S): Homo sapiens

SUBMITTER: Cuiping CHI

PROVIDER: E-GEOD-34131 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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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Gene expression profile of peripheral blood leukocytes of 60Co gamma-ray accidently-irradiated persons

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