TPM-C2 - Radiobiology - Biological Response Orlando VI 16:00 - 17:15
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| Chair(s): Ronald Goans, Lisa Manglass
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TPM-C2.1
16:00 The Neutrophil-Lymphocyte Ratio as a Triage Tool – The REAC/TS Accident Registry Experience RE Goans*, MJW Corporation
Abstract: In triage after a radiation event, it is necessary to decide whether a patient has experienced a clinically significant dose (> 2 Gy) which would require referral for additional evaluation and possible treatment. This is a binary decision, yes or no. The neutrophil to lymphocyte ratio (NLR) is such a decision parameter, is simple to obtain in field operations and is recognized in clinical medicine as an independent marker of systemic inflammation. NLR is evaluated for usefulness in triage using data from the REAC/TS Radiation Accident Registry. A radiation accident data set has been prepared using historic complete blood counts from 10 criticality events (27 patients) and 29 gamma events (45 patients). A cohort of 125 normal controls has also been assembled for comparison with the published radiation accident data. In the control set NLR is found to be 2.1 ± 0.06 (mean ± SEM) and distributed consistent with a Gaussian distribution. In the well-documented Y-12 criticality accident (1958), NLR is statistically elevated above controls from < 4 h until 14 d post-event. For times > 14 d post-event, NLR is less than the control value. This unexpected result has been confirmed using late hematological data taken from patients at Hiroshima and Nagasaki and appears to be a general finding. Since triage is a binary decision, analyzing NLR with receiver operating curve (ROC) statistics is appropriate. The Youden J statistic (sensitivity + specificity -1) is used to determine an appropriate decision point for dose positivity. For this dataset, the decision point for NLR is found to be 2.72, with area under the curve (AUC) 0.881, sensitivity 0.85, specificity 0.86, positive predictive value (PPV) 0.50, and negative predictive value (NPV) 0.97. Therefore, when a known radiation event has occurred and if the patient's NLR is greater than 2.72 early post-event, then that person should be referred for further health physics and medical evaluation.
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TPM-C2.2
16:15 Uptake of 239Pu in Common Environmental Bacteria Evaluated for Transcriptional Changes as a Result of Low-Dose Radiological Exposures LM Manglass*, Clemson University
; M Wintenberg, Clemson University; M Blenner, Clemson University; N Martinez, Clemson University
Abstract: The objective of this work is to determine the feasibility of distinguishing between different radionuclide sources using transcriptional changes in microbial systems that are commonly found in the environment. Microbial systems have the potential to monitor and report on nuclear activities while being both unattended and capable of reporting on these activities even after a source has been moved or relocated. Liquid cultures of Escherichia coli and Pseudomonas putida were exposed to 239Pu and 55Fe that was added directly to liquid cultures both individually and in combination. To effectively use these bacteria species as biosensors, an understanding of the dose-response relationship is critical. The path length of 239Pu alpha emissions in water is similar to the average size of both E. coli and P. putida cells, such that 239Pu that concentrates in cells via uptake or sorption is relevant to the cell dose in liquid cultures. This presentation will focus on the comparative uptake of 239Pu under a variety of conditions, focusing on two main factors. The first factor considered is the presence of citrate, which was used as a complexing agent to improve 239Pu solubility. The second factor was the addition of 55Fe, as iron is a micronutrient for cells. The results of the project discuss the uptake of 239Pu in liquid cultures of bacteria and what insights the uptake studies offered when examining transcriptional changes observed by differential gene expression at multiple time points in 30-day studies. This work strives to advance of our understanding of the impact of low-dose radiation on microbial systems, which has a high applicability to the field of nuclear forensics and non-proliferation.
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TPM-C2.3
16:30 The Pseudo Pelger-Huet Anomaly as a Potential Biodosimeter for Chronic Low Dose Radiation Exposures of Japanese Wild Boar JM Hayes*, Colorado State University
; C Iddins, Oak Ridge Associated Universities; TE Thomas, Colorado State University; R Goans, Oak Ridge Associated Universities; Hayes
Abstract: On March 11, 2011 a 9.0 earthquake struck off the east coast of Japan, resulting in a near 20-foot Tsunami that devastated the coastline. Among the damage was the Fukushima-Daiichi nuclear reactor which over pressurized, due to failed cooling systems, leading to the release of a plume of radionuclides into the surrounding environment that included Iodine-131, Cesium-134, and Cesium-137. The people of the region were immediately evacuated, many of whom have still not returned to the exclusion zone, leaving nature to take over. Many wildlife populations, including the Large Japanese Field Mouse (Apodemus speciosus) and Wild Boar (Sus scrofa leucomystax) have begun to thrive in the region largely due to the absence of human influence. The contaminated environment in which these animals live provides a unique opportunity for radiobiological research involving chronic low dose exposures, similar to those that human inhabitants of Fukushima Prefecture and radiation workers are likely to experience. Here, quantitative bio-dosimetry was employed to evaluate environmental radiation exposure in two wildlife species. Specifically, frequencies of abnormal neutrophils referred to as pseudo Pelger-Huët anomalies (PPHAs) in peripheral blood of the large Japanese field mouse and wild boar living in exclusion zone and control zones. PPHAs have been shown to be informative biomarkers of radiation exposure in several scenarios, including archived slides from the 1958 Y-12 criticality accident, the radium dial painters from the first half of the 20th century, and chronically exposed bats in South African caves containing high levels of thorium. The PPHA morphology was indeed confirmed in the blood of exposed wild boars, however PPHAs did not occur in the large Japanese field mouse. Since confirmation of the presence of the morphology in wild boars, 101 new boars have been collected for both PPHA analysis and dicentric chromosome analysis.
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TPM-C2.4
16:45 Detection of Early Radiation Damage to the Eye-Lens of Rainbow Trout M Kocemba*, University of Ontario Institute of Technology
; AJ Waker, University of Ontario Institute of Technology
Abstract: The objective of this work is to contribute to the study of radiation effects in non-human biota and potentially to the study of eye-lens damage in humans by investigating the effects of low-energy x-rays on the lenses of rainbow trout (Onchorhynchus mykiss). The lenses were cultured ex vivo and irradiated to doses up to 0.34 Gy with low-energy x-rays of 40 kV and a half-value thickness of 0.2 mm in polyethylene terephthalate for an uncollimated beam. A laser focal analysis system was used to track changes in focal lengths across the lenses from pre-irradiation up to one week post-irradiation. Measuring changes in lens focal length variability (FLV) is a standard method employed in ophthalmology and toxicology, and the purpose of this study was to determine whether FLV could give an indication of the early effects of radiation on lens health. Five dose points between 0.04 Gy to 0.34 Gy were observed. None of the groups showed differences in focal length variability compared to the control group (FLV of 0.12 mm +/- 0.02 mm for the 0.34 Gy group compared to 0.11 mm +/- 0.01mm for the control group), but the higher dose groups showed some increase in epithelial clouding (a separate indicator of damage). The experiment will be continued with progressively higher doses in order to determine the onset of observable changes in lens refraction capability.
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TPM-C2.5
17:00 Comparative Analysis of The Effect of Low Doses of Radiation on Human Mesenchymal Stem Cells. DY Usupzhanova*, State Research Center - Burnasyan Federal Medical Biophysical Center FMBA of Russia
; TA Astrelina, State Research Center - Burnasyan Federal Medical Biophysical Center FMBA of Russia; VA Nikitina, State Research Center -Burnasyan Federal Medical Biophysical Center FMBA of Russia; YB Suchkova, State Research Center - Burnasyan Federal Medical Biophysical Center FMBA of Russia; IV Kobzeva, State Research Center - Burnasyan Federal Medical Biophysical Center FMBA of Russia; VA Brunchukov, State Research Center - Burnasyan Federal Medical Biophysical Center FMBA of Russia; VA Brumberg, State Research Center - Burnasyan Federal Medical Biophysical Center FMBA of Russia; VY Nugis, State Research Center - Burnasyan Federal Medical Biophysical Center FMBA of Russia; AN Osipov, State Research Center - Burnasyan Federal Medical Biophysical Center FMBA of Russia; AS Samoylov, State Research Center - Burnasyan Federal Medical Biophysical Center FMBA of Russia
Abstract: Throughout life, a person is constantly exposed to low doses of radiation. However, despite the prevalence and severity of the effects of radiation on the body, to date, its effects on stem cells of humans (regenerative reserve) have not been studied. Thus, the aim of this work was to study the effect of low doses of radiation on mesenchymal stem cells (MSC) from various sources to assess the long-term effects in vitro.
After exposure of MSC mucosal gum tissue at a dose of 80 mGy (X-ray irradiation, power of 100 kV of 40 mGy/min) an increase in the level of proliferative activity, stability of the levels of surface antigens (AG) (CD73 and D105), and a significant decrease in the number of chromosomal aberrations compared with the control group during prolonged cultivation were observed. Following exposure of MSCs of the placenta, the following results were observed: the levels of CD73 and CD105 were decreased at doses of 250 and 1,000 mGy in long-term culture, whereas proliferative activity was increased at a dose of 1,000 mGy. Following exposure of MSCs of the corneal limbus, levels of CD73 and CD105 were increased after irradiation at a dose of 80 mGy and the levels of all AG for all doses in long-term culture were increased, except for a decrease in the levels of СD73 (along with proliferative activity) at a dose of 80 mGy. Following exposure of MSC of the bone marrow, the number of double-stranded breaks DNA were slightly increased in the early stages after irradiation at a dose of 80 mGy, but their numbers were increased at a dose of 1,000 mGy in long-term culture both in comparison with the control group and with the group of cells irradiated dose of 80 mGy.
Thus, the results of our study showed that low doses of radiation exposure affect human MSCs. It was found that the effects of the same dose may be different for MSCs from different types of tissues. The effect can be both depressing, in terms of instability levels of AG, a decrease in proliferative activity, and sustained manifestations of chromosomal aberrations, as well as stimulating by the same criteria. These results cannot unambiguously indicate the negative or positive effects of low doses of radiation. Therefore, the presented research will be continued and supplemented.
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