Radiation-induced Signal Research Articles

Preparation and applicability of fresh fruit samples for the identification of radiation treatment by EPR

The results of electron paramagnetic resonance (EPR) study on fresh fruits (whole pulp of pears, apples, peaches, apricots, avocado, kiwi and mango) before and after gamma-irradiation are reported using two drying procedures before EPR investigation. In order to remove water from non-irradiated and irradiated samples of the first batch, the pulp of fresh fruits is pressed, and the solid residue is washed with alcohol and dried at room temperature. The fruits of the second batch are pressed and dried in a standard laboratory oven at 40 °C. The results obtained with both drying procedures are compared. All samples under study show a singlet EPR line with g=2.0048±0.0005 before irradiation. Irradiation gives rise to typical “cellulose-like” EPR spectrum featuring one intensive line with g=2.0048±0.0005 and two very weak satellite lines situated 3 mT at left and right of the central line. Only mango samples show a singlet line after irradiation. The fading kinetics of radiation-induced EPR signal is studied for a period of 50 days after irradiation. When the irradiated fruit samples are stored in their natural state and dried just before each EPR measurement, the satellite lines are measurable for less than 17 days of storage. Irradiated fruit samples, when stored dried, lose for 50 days ca. 40% of their radiation-induced radicals if treated with alcohol or ca. 70% if dried in an oven. The reported results unambiguously show that the presence of the satellite lines in the EPR spectra could be used for identification of radiation processing of fresh fruits, thus extending the validity of European Protocol EN 1787 (2000). Foodstuffs—Detection of Irradiated Food Containing Cellulose by EPR Spectroscopy. European Committee for Standardisation. Brussels for dry herbs.

Electron paramagnetic resonance radiation dosimetry in fingernails

There is now an increased need for accident dosimetry due to the increased risk of significant exposure to ionizing radiation from terrorism or accidents. In such scenarios, dose measurements should be made in individuals rapidly and with sufficient accuracy to enable effective triage. Electron paramagnetic resonance (EPR) is a physical method of high potential for meeting this need, providing direct measurements of the radiation-induced radicals, which are unambiguous signatures of exposure to ionizing radiation. For individual retrospective dosimetry, EPR in tooth enamel is a proven and effective technique when isolated teeth can be obtained. There are some promising developments that may make these measurements feasible without the need to remove the teeth, but their field applicability remains to be demonstrated. However, currently it is difficult under emergency conditions to obtain tooth enamel in sufficient amounts for accurate dose measurements. Since fingernails are much easier to sample, they can be used in potentially exposed populations to determine if they were exposed to life-threatening radiation doses. Unfortunately, only a few studies have been carried out on EPR radiation-induced signals in fingernails, and, while there are some promising aspects, the reported results were generally inconclusive. In this present paper, we report the results of a systematic investigation of the potential use of fingernails as retrospective radiation dosimeters.

DNA-PKcs and ATM influence generation of ionizing radiation-induced bystander signals

The phenomenon by which irradiated cells influence non-irradiated neighboring cells, referred to as the bystander effect (BSE), is not well understood in terms of the underlying pathways involved. We sought to enlighten connections between DNA damage repair and the BSE. Utilizing sister chromatid exchange (SCE) frequencies as a marker of the BSE, we performed cell transfer strategies that enabled us to distinguish between generation versus reception of a bystander signal. We find that DNA-dependent Protein Kinase catalytic subunit (DNA-PKcs) and Ataxia Telangectasia Mutated (ATM) are necessary for the generation of such a bystander signal in normal human cells following gamma (gamma)-ray exposure, but are not required for its reception. Importantly, we also show that directly irradiated human cells do not respond to receipt of a bystander signal, helping to explain why the BSE is a low-dose phenomenon. These studies provide the first evidence for a role of the DNA damage response proteins DNA-PKcs and ATM specifically in the generation of a bystander signal and intercellular signaling.

Detection of γ-Irradiated Sesame Seeds before and after Roasting by Analyzing Photostimulated Luminescence, Thermoluminescence, and Electron Spin Resonance

Sesame seeds were irradiated using a (60)Co irradiator (0-4 kGy) and then roasted (220 degrees C for 10 min). To identify the irradiation treatment, physical detection methods like photostimulated luminescence (PSL), thermoluminescence (TL), and electron spin resonance (ESR) have been investigated before and after roasting. The photon counts of the irradiated samples (nonroasted and roasted) were higher than those of nonirradiated ones, making it possible to distinguish the two samples. The threshold values of nonroasted and roasted samples increased linearly with the irradiation dose, respectively. The TL for the nonirradiated nonroasted and roasted samples presented a lower peak at about 300 degrees C, but irradiated samples showed a higher peak at around 150 degrees C. The areas of TL glow curves were 15 times higher in nonroasted as compared with roasted samples. TL ratio [integrated area of TL 1 (the first glow)/TL 2 (the second glow)] obtained by the reirradiation step was 0 in nonirradiated samples and more than 0.15 in irradiated samples. The radiation-induced ESR signals originating from cellulose were determined in irradiated samples before and after roasting.

Electron paramagnetic resonance in human fingernails: the sponge model implication

The most significant problem of electron paramagnetic resonance (EPR) fingernail dosimetry is the presence of two signals of non-radiation origin that overlap the radiation-induced signal (RIS), making it almost impossible to perform dose measurements below 5 Gy. Historically, these two non-radiation components were named mechanically induced signal (MIS) and background signal (BKS). In order to investigate them in detail, three different methods of MIS and BKS mutual isolation have been developed and implemented. After applying these methods, it is shown here that fingernail tissue, after cut, can be modeled as a deformed sponge, where the MIS and BKS are associated with the stress from elastic and plastic deformations, respectively. A sponge has a unique mechanism of mechanical stress absorption, which is necessary for fingernails in order to perform its everyday function of protecting the fingertips from hits and trauma. Like a sponge, fingernails are also known to be an effective water absorber. When a sponge is saturated with water, it tends to restore to its original shape, and when it loses water, it becomes deformed again. The same happens to fingernail tissue. It is proposed that the MIS and BKS signals of mechanical origin be named MIS1 and MIS2 for MISs 1 and 2, respectively. Our suggested interpretation of the mechanical deformation in fingernails gives also a way to distinguish between the MIS and RIS. The results obtained show that the MIS in irradiated fingernails can be almost completely eliminated without a significant change to the RIS by soaking the sample for 10 min in water. The proposed method to measure porosity (the fraction of void space in spongy material) of the fingernails gave values of 0.46-0.48 for three of the studied samples. Existing results of fingernail dosimetry have been obtained on mechanically stressed samples and are not related to the "real" in vivo dosimetric properties of fingernails. A preliminary study of these properties of pre-soaked (unstressed) fingernails has demonstrated their significant difference from fingernails stressed by cut. They show a higher stability signal, a less intensive non-radiation component, and a nonlinear dose dependence. The findings in this study set the stage for understanding fingernail EPR dosimetry and doing in vivo measurements in the future.

Preliminary OSL studies on beige sepiolites

Radiation-induced luminescence signals in beige sepiolite samples were investigated using optically stimulated luminescence. A thermally stable, light-sensitive radiation-induced signal was detected, and radiation dose response and thermal properties of this signal were studied. The thermal stability and dose sensitivity of the signal implies the potential of the material for dating and retrospective radiation dosimetry.

SU11248 (Sunitinib) Sensitizes Pancreatic Cancer to the Cytotoxic Effects of Ionizing Radiation

SU11248 (sunitinib) is a small-molecule tyrosine kinase inhibitor which targets VEGFR and PDGFR isoforms. In the present study, the effects of SU11248 and ionizing radiation on pancreatic cancer were studied. For in vitro studies human pancreatic adenocarcinoma cells lines were treated with 1 microM SU11248 1 h before irradiation. Western blot analysis was used to determine the effect of SU11248 on radiation-induced signal transduction. To determine if SU11248 sensitized pancreatic cancer to the cytotoxic effects of ionizing radiation, a clonogenic survival assay was performed using 0-6 Gy. For in vivo assays, CAPAN-1 cells were injected into the hind limb of nude mice for tumor volume and proliferation studies. SU11248 attenuated radiation-induced phosphorylation of Akt and ERK at 0, 5, 15, and 30 min. Furthermore, SU11248 significantly reduced clonogenic survival after treatment with radiation (p < 0.05). In vivo studies revealed that SU11248 and radiation delayed tumor growth by 6 and 10 days, respectively, whereas combined treatment delayed tumor growth by 30 days. Combined treatment with SU11248 and radiation further attenuated Brdu incorporation by 75% (p = 0.001) compared to control. SU11248 (sunitinib) sensitized pancreatic cancer to the cytotoxic effects of radiation. This compound is promising for future clinical trials with chemoradiation in pancreatic cancer.

A technique to measure the absorbed dose in human tooth enamel using EPR method

The EPR spectrum of irradiated tooth enamel contains a multitude of signals that are divided into two categories of radiation-induced and radiation insensitive (native) signals. At lower doses the broad native signal obscures the radiation-induced signal. In this work attempt has been made to find a method to measure the radiation-induced signal other than peak-to-peak signal amplitude measurement. For this reason software was programmed to extract the data from EPR system. The average amplitude of the radiation-induced EPR signal which is defined between the known g -values can also be calculated using the software. The result of this calculations were considered as the EPR response for the tooth enamel samples irradiated from 100 to 500 mGy and was drawn as the calibration curve. The resulted data as compared to the peak-to-peak amplitude measurement method seems to be more reproducible and shows a better variation against the dose values.

Numeric experiment for analysis of uncertainty of spectra processing in EPR dosimetry

In dosimetry based on Electron Paramagnetic Resonance (EPR) spectroscopy, radiation doses are evaluated from the analysis of the EPR spectrum. Usually investigators use their own specially designed computer software for extraction of radiation induced signal from the total EPR spectrum and for determination of its intensity. This process is able to discriminate the total spectrum of irradiated material into the radiation induced signal and the non-radiation induced signals. However even after separation of these spectral components the result represents the superposition of true radiation line and a residual noise. The present study is aimed at investigating the process of EPR signal amplitude reconstruction in tooth enamel, one of the most radiation sensitive materials among those used in EPR dosimetry. The specific scope of this paper is the understanding of the influence of the selected model for description of radiation signal, of the fitting method, and of noise variation on the invert restoration of primary signal. Three numerical experiments for simulation of the amplitude reconstruction were performed: 1. Test of models for description of radiation signal: Influence of the complexity of the model for signal reconstruction on the uncertainty of spectra processing was tested. 2. Test of fitting method of radiation signal: Influence of fitting method on the uncertainty of spectra processing was tested. 3. Test on noise and deconvolution influence on specific method of amplitude reconstruction used in DOSEREC software. Modeled cumulative signal was obtained by superposition of modeled radiation signals and simulated random noise. Model of random noise were constructed based on EPR measurements of 156 spectra of tooth samples of Urals rural population. The obtained noise amplitudes include not only white noise but also individual variations of chemical composition of samples and error of preliminary deconvolution. Variation of reconstructed spectra versus simulated spectra gives the information about accuracy of signal processing and about main sources of errors and uncertainties. In this report the results of numeric experiments will be discussed in context of possibility of improvement of spectral analysis. Acknowledgment - This work was supported by project “Southern Urals Radiation Risk Research – SOUL”.

Q-BAND EPR BIODOSIMETRY IN TOOTH ENAMEL MICROSAMPLES: FEASIBILITY TEST AND COMPARISON WITH X-BAND

A comparative study of electron paramagnetic resonance dosimetry in Q- and X-bands has shown that Q-band is able to provide accurate measurements of radiation doses even below 0.5 Gy with tooth enamel samples as small as 2 mg. The optimal amount of tooth enamel for dose measurements in Q-band was found to be 4 mg. This is less than 1% of the total amount of tooth enamel in one molar tooth. Such a small amount of tooth enamel can be harmlessly obtained in an emergency requiring after-the-fact radiation dose measurement. The other important advantage of Q-band is full resolution of the radiation-induced EPR signal from the native, background signal. This separation makes dose response measurements much easier in comparison to conventional X-band measurements in which these overlapping signals necessitate special methods for doses below 0.5 Gy. The main disadvantages of Q-band measurements are a higher level of noise and lower spectral reproducibility than in X-band. The effect of these negative factors on the precision of dose measurements in Q-band could probably be reduced by improvement of sample fixation in the resonance cavity and better optimization of signal filtration to reduce high-frequency noise.

Detection of Free Radicals in Electron Beam-Irradiated Mucuna pruriens (L. DC.) Seeds by Electron Spin Resonance

Electron spin resonance (ESR) spectroscopy was employed to detect free radicals in raw Mucuna pruriens (velvet bean) seeds after electron beam irradiation (Microtron source: 0, 2.5, 5, 7.5, 10, 15 and 30 kGy) and conventional processing (roasting, powdering and cooking). The ESR signal of irradiated seeds (g=2.0055±0.0001) was more prominent in the seed coat than cotyledon. Seed coat of irradiated samples showed dose-dependent linear increase of this signal (g = 2.0055) accompanied by a weak triplet (satellite peak; aH = 3 mT) produced exclusively by radiolysis and could be used as an indication of successful irradiation. Irradiated cotyledon portion devoid of satellite peak (triplet) showed a linear increase in signal intensity up to 10 kGy with a sharp decline at higher doses (15 and 30kGy). Stability of radiation-induced ESR signals after 6 months of storage (25 ± 1°C) revealed the presence of a weak triplet with a substantial loss of signal intensity. Thermal effects such as roasting and powdering of seeds increased the signal intensity (g = 2.0055) similar to or in greater proportion than irradiation. Phenolics in seeds, which contribute significantly to detect free radicals in vegetative parts of a plant showed a waning trend in seed coat, while it was vice versa in cotyledon. Textural studies revealed significant loss in firmness after irradiation (p&lt;0.05), which might favour in minimising the cooking time. Results of the present study might help to divulge the beneficial effects of application of electron beam irradiation technology as a better alternative to fumigants in seed preservation for safety and quarantine purposes.

Solid-state luminescence for the optical examination of archaeological glass beads

The work pertains to the application of solid-state luminescence as a characterization tool for glassy ceramic cultural artefacts. An archaeological glass bead collection excavated at the city of Thebes, Greece and considered as unique in terms of typological variety and time span was examined with the application of luminescence techniques (thermoluminescence, optically stimulated luminescence). Additionally, X-rays fluorescence (XRF) was used to provide non-destructively the elemental concentration profile of the samples. The thermoluminescence signals following laboratory irradiation provided distinct groups of spectra types according to the color classification of the samples. For each sample, the signal sensitivity and growth were examined using both thermoluminescence and optically stimulated luminescence recording. The study provides evidence for the usefulness of the combined application of luminescence and non-destructive, XRF-based, elemental analysis for the characterization of glass assemblages. Finally, due to the satisfactory level of radiation-induced signal intensity, the work suggests the possibility of chronological estimation of ancient glass beads using luminescence dating protocols.

Optically stimulated luminescence (OSL) of dental enamel for retrospective assessment of radiation exposure

This paper briefly reviews the optically stimulated luminescence (OSL) properties of dental enamel and discusses the potential and challenges of OSL for filling the technology gap in biodosimetry required for medical triage following a radiological/nuclear accident or terrorist event. The OSL technique uses light to stimulate a radiation-induced luminescence signal from materials previously exposed to ionizing radiation. This luminescence originates from radiation-induced defects in insulating crystals and is proportional to the absorbed dose of ionizing radiation. In our research conducted to date, we focused on fundamental investigations of the OSL properties of dental enamel using extracted teeth and tabletop OSL readers. The objective was to obtain information to support the development of the necessary instrumentation for retrospective dosimetry using dental enamel in laboratory, or for in situ and non-invasive accident dosimetry using dental enamel in emergency triage. An OSL signal from human dental enamel was detected using blue, green, or IR stimulation. Blue/green stimulation associated with UV emission detection seems to be the most appropriate combination in the sense that there is no signal from un-irradiated samples and the shape of the OSL decay is clear. Improvements in the minimum detection level were achieved by incorporating an ellipsoidal mirror in the OSL system to maximize light collection. Other possibilities to improve the sensitivity and research steps necessary to establish the feasibility of the technique for retrospective assessment of radiation exposure are also discussed.

EPR dosimetry in chemically treated fingernails

By using EPR measurements of radiation-induced radicals it is possible to utilize human fingernails to estimate radiation dose after-the-fact. One of the potentially limiting factors in this approach is the presence of artifacts due to mechanically induced EPR signals (MIS) caused by mechanical stress during the collection and preparation of the samples and the so-called background (non-radiation) signal (BKS). The MIS and BKS have spectral parameters (shape, g -factor and linewidth) that overlap with the radiation-induced signal (RIS) and therefore, if not taken into account properly, could result in a considerable overestimation of the dose. We have investigated the use of different treatments of fingernails with chemical reagents to reduce the MIS and BKS. The most promising chemical treatment (20 min with 0.1 M dithiothreitol aqueous solution) reduced the contribution of MIS and BKS to the total intensity of EPR signal of irradiated fingernails by a factor of 10. This makes it potentially feasible to measure doses as low as 1 Gy almost immediately after irradiation. However, the chemical treatment reduces the intensity of the RIS and modifies dose dependence. This can be compensated by use of an appropriate calibration curve for assessment of dose. On the basis of obtained results it appears feasible to develop a field-deployable protocol that could use EPR measurements of samples of fingernails to assist in the triage of individuals with potential exposure to clinically significant doses of radiation.

Effect of chemical treatment on ESR dosimetry of cow teeth: Application to the samples from Southern Urals

Chemical treatment with alkaline solution is used to extract enamel from teeth for retrospective ESR (EPR) dosimetry. It was confirmed in the present study that our condition of chemical treatment does not affect retrospective doses of cow teeth. The method was applied to 10 teeth collected in the South Ural region where the soil is contaminated with Sr 90 . As a result, no noticeable doses were detected so far. Significant variations of sensitivity of the radiation-induced ESR signal to radiation were found for different cow teeth, indicating that individual calibration is necessary.

Radiation dose reconstruction from L-band in vivo EPR spectroscopy of intact teeth: Comparison of methods

In vivo EPR tooth dosimetry is a more challenging problem than in vitro EPR dosimetry because of several potential additional sources of variation associated with measurements that are made in the mouth of a living subject. For in vivo measurement a lower RF frequency is used and, unlike in the in vitro studies, the tooth cannot be processed to optimize the amount and configuration of the enamel that is measured. Additional factors involved with in vivo measurements include the reproducibility of positioning the resonator on the surface of the tooth in the mouth, irregular tooth geometry, and the possible influence of environmental noise. Consequently, in addition to using the theoretical and empirical models developed for analyzing data from measurements of teeth in vitro, other unconventional and more robust methods of dose reconstruction may be needed. The experimental parameter of interest is the peak-to-peak amplitude of the spectrum, which is correlated to the radiation dose through a calibration curve to derive the reconstructed dose. In this study we describe and compare the results from seven types of computations to measure the peak-to-peak amplitude for estimation of the radiation-induced signal. The data utilized were from three sets of in vivo measurements of irradiated teeth. Six different teeth with different doses were placed in the mouth of a volunteer in situ and measurements of each tooth were carried out on three different days. The standard error of prediction (SEP) is used as a figure of merit for quantifying precision of the reconstruction. We found that many of the methods gave fairly similar results, with the best error of prediction resulting from a computation based on a Lorentzian line model whose center field corresponds to the known parameter of the radiation-induced EPR spectra of teeth, with corrections from a standard sample that was measured as part of the data acquisition scheme. When the results from the three days of measurement were pooled, the SEP decreased dramatically, which suggests that one of the principal sources of variation in the data is the ability to precisely standardize the measurement conditions within the mouth. There are very plausible ways to accomplish improvements in the existing procedures.

Analysis of EPR tooth enamel spectra exposed to combined radiation and mechanical effects

In the EPR spectra of tooth enamel samples exposed to sequential radiation and mechanical effect, the intensity of the signal in the spectra of tooth enamel samples exposed to sequential mechanical and radiation effects exceeded the amplitude of a signal in enamel samples that were only exposed to radiation. The increased dosimetric signal can be explained by superposition of mechanically and radiation-induced signals. The contribution of the mechanically induced component to the individual dose load reconstructed by EPR-spectra of tooth enamel has been evaluated.

Current Concepts for the Combined Treatment Modality of Ionizing Radiation with Anticancer Agents

In current applied radiobiology, there exists a tremendous effort in basic and translational research to identify novel treatment modalities combining ionizing radiation with anticancer agents. This is mainly due to the highly improved molecular understanding of intrinsic radioresistance and the profiling of cellular stress responses to irradiation during recent years. Ionizing radiation not only damages DNA but also affects multiple cellular components that induce a multi-layered stress response. The treatment responses can be restricted to the individual cell level but might also be part of an intercellular stress communication network. Both DNA damage-induced signaling (which results in cell cycle arrest and induction of the DNA-repair machinery) and also ionizing radiation-induced signal transduction cascades, which are generated at cellular sites distant from and independent of DNA-damage, represent interesting targets for anticancer treatment modalities to sensitize for ionizing radiation. Due to the lack of molecular knowledge classic radiobiology assembled the cellular and tissue responses into four groups (4 R's of radiotherapy) which describe biological factors influencing the treatment response to fractionated radiotherapy. These classic 4 R's are Repair, Reassortment, Repopulation and Reoxygenation. With the tremendous progress in molecular oncology we now begin to understand theses factors on the molecular level. At the same time this classification may guide modern molecular radiobiologists to identify novel pharmaceuticals and antisignaling agents which can modulate the treatment response to irradiation. In this review we describe current approaches to sensitize tumor cells with novel anticancer agents along the lines of these 4 R's.

Communication of Radiation-Induced Stress or Bystander Signals between Fish in Vivo

We report data in this paper suggesting that fish irradiated to 0.5 Gy total body dose can release factors into the water that signal other unexposed fish and cause induction of bystander effects expressed as increased cell death in a reporter system. Radiation-induced bystander effects, resulting in the appearance of radiation damage or induction of typical radiation responses in unirradiated cells and tissues are now an established consequence of exposure to low doses of ionizing radiation, however little work has been done in vivo or in species other than humans or mice. In these experiments rainbow trout were irradiated and then paired with unirradiated fish for two hours. Additionally, unirradiated fish were placed in water which had previously been used to hold irradiated fish for 2 h. Sham-irradiated fish and absolute control fish were also examined all using blind protocols. Following a two h incubation period, at these various exposure regimes, the fish were killed by a blow to the head and dissected. Five organs were removed from each fish and tissue explants were cultured using an established technique. After 2 days, the culture medium was harvested and used in a reporter assay to determine whether a bystander effect had been induced. The explants were cultured on in Clonetics growth medium for a further 14 days then fixed for assay of radiation response proteins. The responses varied according to the cell type in the original explants, with the gill and fin showing the most pronounced response. The results suggest that communication signals leading to a typical radiation response can be passed between fish and seem to involve secretion of a chemical messenger into the water.

The effect of heating on background and radiation-induced EPR signals in tooth enamel

The presented study is a continuation of our work performed during participation in the Third International Intercomparison on EPR Tooth Dosimetry. During the process of samples preparation, all 22 enamel samples were accidentally exposed for about 30 min to 150 °C temperature. This considerably affected shape of their EPR spectra mainly due to substantial increase in the background signal, which approximately doubled its contribution to the spectra. These effects were studied closer under controlled conditions of the delivered dose and heating temperature using another enamel samples. The observed changes in the spectra shape partially faded within a few days after heating. The heating resulted also in a noticeable generation of a spectral component similar to the dosimetric signal induced in enamel by radiation. The temperature-induced dosimetric component in EPR spectra of the heated samples remained constant for 32 days. Deviations in calculated contributions of the dosimetric signal into total EPR spectra of irradiated sample varied from −12 to +15% of its initial contribution in the non-heated enamel, depending on type of the background spectrum applied in numerical processing of the spectra.