Micronucleated CD71-positive reticulocytes: a blood-based endpoint of cytogenetic damage in humans

Dertinger, Stephen D.; Chen, Yuhchyau; Miller, Richard K.; Brewer, Kelly; Smudzin, T.; Torous, Dorothea K.; Hall, Nikki E.; Olvany, Kristine A.; Murante, Francis G.; Tometsko, Carol R.

doi:10.1016/j.mrgentox.2003.08.004

Cited by 50 publications

(36 citation statements)

References 38 publications

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“…A number of alternative minimally invasive strategies have been explored, including the measurement of specific cytokines and metabolites in tissues and body fluids (4), micronucleus assays (13), and germ line radiation-induced apoptosis rates (2). More recently, a need for comprehensive profiling in the field of biomarker discovery has been recognized (10,14).…”

Section: Introductionmentioning

confidence: 99%

Discovering Clinical Biomarkers of Ionizing Radiation Exposure with Serum Proteomic Analysis

et al. 2006

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In this study, we sought to explore the merit of proteomic profiling strategies in patients with cancer before and during radiotherapy in an effort to discover clinical biomarkers of radiation exposure. Patients with a diagnosis of cancer provided informed consent for enrollment on a study permitting the collection of serum immediately before and during a course of radiation therapy. High-resolution surfaceenhanced laser desorption and ionization-time of flight (SELDI-TOF) mass spectrometry (MS) was used to generate high-throughput proteomic profiles of unfractionated serum samples using an immobilized metal ion-affinity chromatography nickel-affinity chip surface. Resultant proteomic profiles were analyzed for unique biomarker signatures using supervised classification techniques. MS-based protein identification was then done on pooled sera in an effort to begin to identify specific protein fragments that are altered with radiation exposure. Sixty-eight patients with a wide range of diagnoses and radiation treatment plans provided serum samples both before and during ionizing radiation exposure. Computer-based analyses of the SELDI protein spectra could distinguish unexposed from radiation-exposed patient samples with 91% to 100% sensitivity and 97% to 100% specificity using various classifier models. The method also showed an ability to distinguish high from low dose-volume levels of exposure with a sensitivity of 83% to 100% and specificity of 91% to 100%. Using direct identity techniques of albuminbound peptides, known to underpin the SELDI-TOF fingerprints, 23 protein fragments/peptides were uniquely detected in the radiation exposure group, including an interleukin-6 precursor protein. The composition of proteins in serum seems to change with ionizing radiation exposure. Proteomic analysis for the discovery of clinical biomarkers of radiation exposure warrants further study. (Cancer Res 2006; 66(3): 1844-50)

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Section: Introductionmentioning

confidence: 99%

Discovering Clinical Biomarkers of Ionizing Radiation Exposure with Serum Proteomic Analysis

et al. 2006

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“…Because of concerns of increased infections risks after total splenectomy in children [13][14][15][16], interest has developed in the use of partial splenectomy to augment HSC transplantation. Initial clinical evidence suggests that partial splenectomy in children with congenital hemolytic anemias may preserve enough splenic tissue to maintain some splenic function, as assessed by the clearance of erythrocytes containing Howell-Jolly bodies, maintenance of serum IgM and IgG levels, and radionuclide uptake by liver-spleen scan [17][18][19][20][21][22][23][24][25][26]. Our initial experience with 5 children who underwent pretransplantation partial splenectomy compares favorably with those who underwent total splenectomy (n = 10), with both procedures resulting in a shorter time to HSC engraftment compared with age-matched nonsplenectomized children (n = 497) [7].…”

Section: Discussionmentioning

confidence: 99%

Splenectomy and partial splenectomy improve hematopoietic stem cell engraftment in hypersplenic mice

Tracy

Talbot

Kurtzberg

et al. 2010

Journal of Pediatric Surgery

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“…This has precluded erythrocytebased analyses from effectively measuring chromosome damage in the past. Dertinger et al [2003] described a high-throughput, single-laser flow cytometric system for scoring the incidence of MN-RET in human blood by differential staining of these cells with anti-CD71-FITC plus propidium iodide and RNase (a similar system is used in this report). Incorporation of an anti-CD42b-PE into the procedure permits the exclusion of platelets (which can interfere with analysis).…”

Section: Discussionmentioning

confidence: 99%

Flow cytometric scoring of micronucleated reticulocytes as a possible high‐throughput radiation biodosimeter

Liu

et al. 2009

Environ and Mol Mutagen

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Micronucleated reticulocyte (MN-RET) scoring by flow cytometry (FCM) has been used in assessment of the clastogenic effects of chemicals. However, its dose-response to acute whole body irradiation (WBI) at moderate dose rates remains to be established. We show that FCM scoring of MN-RET in peripheral blood from male ICR mice exposed to WBI X-ray doses of 0.5-5 Gy at a dose rate of 0.488 Gy/min exhibits a linear dose-response relationship 24, 48, and 72 hr following WBI. Parallel microscopic counting of micronucleated polychromatic erythrocytes (MN-PCE) in bone marrow smears from the same animals showed similar linear dose-response patterns at the same time points. Indeed, MN-RET and MN-PCE were highly correlated at all doses and time points. In view of the speed and accuracy of this method, in addition to the small blood sample size needed for the assay, the flow cytometric protocol for MN-RET scoring may provide a minimally-invasive, high throughput radiation biodosimeter.

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Micronucleated CD71-positive reticulocytes: a blood-based endpoint of cytogenetic damage in humans

Cited by 50 publications

References 38 publications

Discovering Clinical Biomarkers of Ionizing Radiation Exposure with Serum Proteomic Analysis

Discovering Clinical Biomarkers of Ionizing Radiation Exposure with Serum Proteomic Analysis

Splenectomy and partial splenectomy improve hematopoietic stem cell engraftment in hypersplenic mice

Flow cytometric scoring of micronucleated reticulocytes as a possible high‐throughput radiation biodosimeter

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