Candidate protein biodosimeters of human exposure to ionizing radiation

Marchetti, Francesco; Coleman, Matthew A.; Jones, Irene M.; Wyrobek, Andrew J.

doi:10.1080/09553000600930103

Cited by 159 publications

(115 citation statements)

References 278 publications

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“…Using skin biopsies from radiotherapy patients, Goldberg and colleagues identified low-dose genes, their variability and functional groups [39][40][41]. A proteomic survey identified several proteins that were phosphorylated or modulated at doses below 10 cGy in a variety of model systems [42]. These studies demonstrate that doses of 1 cGy of low-linear energy transfer (LET) radiation (~0.3 double strand breaks per cell) are sufficient to modulate gene expression.…”

Section: Introductionmentioning

confidence: 99%

Low dose radiation response curves, networks and pathways in human lymphoblastoid cells exposed from 1 to 10cGy of acute gamma radiation

Wyrobek

Manohar

Krishnan

et al. 2011

Mutation Research/Genetic Toxicology and Environmental Mutagene

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We investigated the low dose dependency of the transcriptional response of human cells to characterize the shape and biological functions associated with the dose response curve and to identify common and conserved functions of low dose expressed genes across cells and tissues.Human lymphoblastoid (HL) cells from two unrelated individuals were exposed to graded doses of radiation spanning the range of 1-10 cGy were analyzed by transcriptome profiling, qPCR and bioinformatics, in comparison to sham irradiated samples. A set of ~80 genes showed consistent responses in both cell lines; these genes were associated with homeostasis mechanisms (e.g., membrane signaling, molecule transport), subcellular locations (e.g., Golgi, and endoplasmic reticulum), and involved diverse signal transduction pathways. The majority of radiation-modulated genes had plateau-like responses across 1-10 cGy, some with suggestive evidence that transcription was modulated at doses below 1 cGy. MYC, FOS and TP53 were the major network nodes of the low-dose response in HL cells. Comparison our low dose expression findings in HL cells with those of prior studies in mouse brain after whole body exposure, in human keratinocyte cultures, and in endothelial cells cultures, indicates that certain components of the low dose radiation response are broadly conserved across cell types and tissues, independent of proliferation status.

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Section: Introductionmentioning

confidence: 99%

Low dose radiation response curves, networks and pathways in human lymphoblastoid cells exposed from 1 to 10cGy of acute gamma radiation

Wyrobek

Manohar

Krishnan

et al. 2011

Mutation Research/Genetic Toxicology and Environmental Mutagene

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“…Recently, several new biodosimetric methods overcoming some of these limitations have been proposed, including protein marker (e.g. H2AX) or serum protein analyses (1,10,17). Nevertheless, these assays are being developed and have not yet been tested in a real triage situation (1).…”

Section: University Of Defence Faculty Of Militarymentioning

confidence: 99%

Cytokinesis-Block Micronucleus (Cbmn) Assay/CBMN Cytome Assay in Human Lymphocytes After in Vitro Irradiation and Its Use in Biodosimetry

Pejchal¹,

Vasilieva²,

Hristozova³

et al. 2011

MMSL

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SummaryAim: Cytokinesis-block micronucleus (CBMN) assay and its comprehensive variant CBMN cytome assay are cytogenetic methods. CBMN is based on assessment of micronuclei in nucleated cells that have completed only one nuclear division. Besides micronuclei, CBMN cytome assay analyzes additional genotoxic (nucleoplasmic bridges and nuclear buds), cytostatic (nuclear division index), and cytotoxic (amount of necrotic and apoptotic cells) parameters. The aim of this study is to evaluate these parameters in human blood lymphocytes after in vitro irradiation and to assess its contribution to biodosimetry. Material and methods: Human blood from 6 donors was in vitro irradiated by 0, 1, 2, 3, 4, or 5 Gy and cultivated for 72 hours. Blood lymphocytes were stimulated with phytohemagglutinin and their cytokinesis was blocked by cytochalasin B. After cultivation, cultures were hypotonically treated, dropped onto glass slides and stained with Giemsa. Slides were evaluated by microscope. Results: We observed significantly increased amount of micronuclei, nucleoplasmic bridges, and nuclear buds measured in binucleated cells, significantly increased amount of micronuclei measured in mononucleated cells and significantly decreased nuclear division index after irradiation by 1, 2, 3, 4, and 5 Gy. Amount of death cells (apoptotic and necrotic) significantly increased after irradiation by 4 and 5 Gy. Conclusion: Although all parameters assessed by CBMN cytome assay have biodosimetric potential, practically feasible is only evaluation of micronuclei in binucleated cells. This parameter was used to construct in vitro linear-quadratic dose-response calibration curve which could be used as a biodosimetric tool for triage of radiation casualties.

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“…Effects of radiation has already been studied in case of phosphorylation [6,[11][12][13], acetylation [12], ubiquitination [14], carbonylation [15,16], nitrosylation [15,16] and glycosylation [17][18][19][20] in different tissues and biofluids and in some cases significant alterations were found.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, radiation may induce changes in higher order organisms. Beside genetics, proteomics may offer new insights, describing new pathophysiological pathways or discovering new biomarker candidates [4][5][6][7][8][9][10] to assess the influence of radiation on living, multicellular organisms. Note, that especially in multicellular organisms, the long-term response of the organism to radiation may even be more important, than radiation damage itself.…”

Section: Introductionmentioning

confidence: 99%

Changes of protein glycosylation in the course of radiotherapy

Tóth

Vékey

Ozohanics

et al. 2016

Journal of Pharmaceutical and Biomedical Analysis

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This is the first study of changes in protein glycosylation due to exposure of human subjects to ionizing radiation. Site specific glycosylation patterns of 7 major plasma proteins were analyzed; 171 glycoforms were identified; and the abundance of 99 of these was followed in the course of cancer radiotherapy in 10 individual patients. It was found that glycosylation of plasma proteins does change in response to partial body irradiation (~60 Gy), and the effects last during follow-up; the abundance of some glycoforms changed more than twofold. Both the degree of changes and their time-evolution showed large inter-individual variability. HIGHLIGHTS: first human study to show that ionizing radiation does change protein glycosylation  glycosylation of 7 major plasma proteins in 10 individual cases were followed  changes of protein glycosylation in response to radiotherapy last for several weeks

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Candidate protein biodosimeters of human exposure to ionizing radiation

Cited by 159 publications

References 278 publications

Low dose radiation response curves, networks and pathways in human lymphoblastoid cells exposed from 1 to 10cGy of acute gamma radiation

Low dose radiation response curves, networks and pathways in human lymphoblastoid cells exposed from 1 to 10cGy of acute gamma radiation

Cytokinesis-Block Micronucleus (Cbmn) Assay/CBMN Cytome Assay in Human Lymphocytes After in Vitro Irradiation and Its Use in Biodosimetry

Changes of protein glycosylation in the course of radiotherapy

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