Unknown,Transcriptomics,Genomics,Proteomics

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Dose- and time- dependent ionizing ratidation effect on mice peripheral blood

ABSTRACT: Gene expression profiles of peripheral blood samples from C57BL/6 mice exposed with ionizing radiation. We used mice as model animal to study biologial recovery response after radiation damage. Therefore, we obtained gene expression profiles from C57BL/6 mice exposed with various levels of ionizing radiation, including low and high doses and control groups. In order to measure recovery rate, we collected peripheral blood samples at different time durations after the exposure. In order to obtain robust signatures specific to radiation response, we are interested in knowing if the radiation signarures will be present in the presence of confounders. Therefore, mice were given intraperitoneal injections of lipopolysaccharide endotoxin (LPS), or treated with granulocyte colony-stimulating factor (GCSF), otherwise no treatment after ionizing radiation exposure. The underlying mechanism of confounder treatment is that LPS induces strong immune response resembling the effect of infection, and GCSF stimulates mobilization of HSCs. Exploratory analysis shows that the confounding effects did affect the radiation signature to some extent. This study provides insights into the molecular basis of time- and dose- dependent response to ionizing radiation in mice hematopoietic system. A total of 536 C57BL/6 mice peripheral blood gene expression profiles were measured in 3 different batches using the Affymetrix mouse 430A 2.0 microarray. The experiment is designed to assess blood gene expression changes after exposure to ionizing radiation of 0, 100, 150, 200, 300, 450, 600, 800 and 1050 cGy. Samples were collected at 6, 24, 48, 72, 120 and 168hrs after a single dose exposure.

ORGANISM(S): Mus musculus

SUBMITTER: lingling zheng

PROVIDER: E-GEOD-52403 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The development of a biodosimetric assay based on the combined gene expression analysis of ex vivo-irradiated human peripheral blood (PB) and humans treated with total body irradiation has been developed. Gene expression profile signature of human radiation injury into a rapid and high-throughput chemical ligation-dependent probe amplification assay (CLPA) has been shown to discriminate 6 radiation dose levels in human PB. Candidate gene lists were first developed assaying human ex vivo and human TBI samples on the Affymetrix platform. For the Ex Vivo samples, healthy consented adult donor was randomly assigned to a radiation group and labeled with the target dose of 0 cGy, 150 cGy, 300 cGy, or 600 cGy. In addition to the radiation exposures, the samples were also treated with either no treatment, GCSF, or LPS at time points 6 hours and 24 hours. Radiation expire times from the Cs137 irradiator were calculated to achieve target doses specific for tubes filled with blood and inserted in the roaring test tube holder. The dose rate was 480 cGy/min for the duration of the study. The healthy donors were enrolled to participate in this study following a protocol to collect PB samples that was previously approved by the Duke University Institutional Review Board. For the TBI samples, adult patients, ages 21 to 66, were evaluated at the Duke University Adult Bone Marrow Transplantation Program enrolled in a Duke IRB-approved protocol to collect PB prior to and post TBI conditioning. With approval from the Duke University Institutional Review Board (IRB), between 5-12 mL of peripheral blood was collected from consented patients prior to and 6 hours following TBI with 150-200 cGy as part of their pre-transplantation conditioning. All patients receiving non-myeloablative conditioning were treated with 200 cGy of TBI from a linear accelerator at a dose rate of 20 cGy/min. All patients who underwent TBI-based myeloablative allogeneic or autologous stem-cell transplantation received radiation fractionated at 150 cGy per fraction at 20 cGy/min. All patients had PB collected (50 ml) prior to and 6 hours following exposure to either 200 cGy or 150 cGy radiation treatment. The dose exposure for TBI patients used in this study were 0 cGy, 150 cGy, 450 cGy and 1050 cGy at 0, 6, 30 and 78 hours post irradiation. Total RNA was extracted and assayed on the Affymetrix platform.

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Dose- and time- dependent ionizing ratidation effect on mice peripheral blood

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