Human Radiation Exposure Research Articles

Pathology of fractionated whole-brain irradiation in rhesus monkeys ( Macaca mulatta ).

Fractionated whole-brain irradiation (fWBI), used to treat brain metastases, often leads to neurologic injury and cognitive impairment. The cognitive effects of irradiation in nonhuman primates (NHP) have been previously published; this report focuses on corresponding neuropathologic changes that could have served as the basis for those effects in the same study. Four rhesus monkeys were exposed to 40 Gy of fWBI [5 Gy × 8 fraction (fx), 2 fx/week for four weeks] and received anatomical MRI prior to, and 14 months after fWBI. Neurologic and histologic sequelae were studied posthumously. Three of the NHPs underwent cognitive assessments, and each exhibited radiation-induced impairment associated with various degrees of vascular and inflammatory neuropathology. Two NHPs had severe multifocal necrosis of the forebrain, midbrain and brainstem. Histologic and MRI findings were in agreement, and the severity of cognitive decrement previously reported corresponded to the degree of observed pathology in two of the animals. In response to fWBI, the NHPs showed pathology similar to humans exposed to radiation and show comparable cognitive decline. These results provide a basis for implementing NHPs to examine and treat adverse cognitive and neurophysiologic sequelae of radiation exposure in humans.

Gamma-spectrometric measurement of radioactivity in agricultural soils of the Lombardia region, northern Italy

This work is part of a wider monitoring project of the agricultural soils in Lombardia, which aims to build a database of topsoil properties and the potentially toxic elements, organic pollutants and gamma emitting radionuclides that the topsoils contain. A total of 156 agricultural soils were sampled according to the LUCAS (Land Use/Cover Area frame statistical Survey) standard procedure. The aim was to provide a baseline to document the conditions present at the time of sampling. The results of the project concerning soil radioactivity are presented here. The aim was to assess the content of 238U, 232Th, 137Cs and 40K by measuring soil samples by gamma spectrometry.238U, 232Th and 40K activities range 24–231, 20–70, and 242–1434 Bq kg−1 respectively. The geographic distribution of 238U reflects the geophysical framework of the Lombardia region: the soils with high content of uranium are distributed for the most part in the South Alpine belt, where the presence of magmatic rocks is widespread. These soils show an higher activity of 238U than of 232Th. The 238U activities become lower than 232Th when soils are located in the plain, originating from basic sedimentary rocks.137Cs activity ranges 0.4–86.8 kBq m−2. The lowest activity of 137Cs is in the plain, whereas the highest is in the North on soils kept as lawn or pasture. The 137Cs activity of some samples suggests the presence of accumulation processes that lead to 137Cs enriched soils.This is the first survey of gamma emitting radionuclides in Lombardia that is based on the LUCAS standard sampling. The results from this monitoring campaign are important for the human radiation exposure and provide the zero point, which will be useful for assessing future effects due to external factors such as human activities.

Annexin V FITC conjugated as a radiation toxicity indicator in lymphocytes following radiation overexposure in radiotherapy programs.

Background:Following human radiation exposure in hospital or accidents, dose assessments are of prime importance in radiation accidents. These issues are of continuing importance with respect to socioeconomic policy relating to the industrial and medical uses of ionizing radiation, and also for risk assessment among people who are occupationally exposed to low and/or high linear energy transfer (LET) radiation, such as astronauts, pilots, stewardesses, nuclear power plant workers, and victims of radiation accidents.Materials and Methods:In this study, an assay for assessing radiation dose based on the induction of apoptosis in human T-lymphocytes was done to examine T-lymphocyte cells isolated from the fresh blood of 16volunteers, cultured and exposed to gamma rays. Radiation-induced apoptosis (RIA) was assessed by flow cytometric identification of cells displaying apoptosis-associated DNA condensation.Results:Dose-response experiments showed that at 2Gy dose level of radiotherapy programs, the RIA frequency was significantly above control. Apoptotic levels significantly depend on the dose of radiation rather than the donor.Conclusion:The results demonstrate the potential use of this assay as a biological indicator of radiation toxicity, optimizing patient dose in radiotherapy and biological dosimetry process.

A translatable predictor of human radiation exposure.

Terrorism using radiological dirty bombs or improvised nuclear devices is recognized as a major threat to both public health and national security. In the event of a radiological or nuclear disaster, rapid and accurate biodosimetry of thousands of potentially affected individuals will be essential for effective medical management to occur. Currently, health care providers lack an accurate, high-throughput biodosimetric assay which is suitable for the triage of large numbers of radiation injury victims. Here, we describe the development of a biodosimetric assay based on the analysis of irradiated mice, ex vivo-irradiated human peripheral blood (PB) and humans treated with total body irradiation (TBI). Interestingly, a gene expression profile developed via analysis of murine PB radiation response alone was inaccurate in predicting human radiation injury. In contrast, generation of a gene expression profile which incorporated data from ex vivo irradiated human PB and human TBI patients yielded an 18-gene radiation classifier which was highly accurate at predicting human radiation status and discriminating medically relevant radiation dose levels in human samples. Although the patient population was relatively small, the accuracy of this classifier in discriminating radiation dose levels in human TBI patients was not substantially confounded by gender, diagnosis or prior exposure to chemotherapy. We have further incorporated genes from this human radiation signature into a rapid and high-throughput chemical ligation-dependent probe amplification assay (CLPA) which was able to discriminate radiation dose levels in a pilot study of ex vivo irradiated human blood and samples from human TBI patients. Our results illustrate the potential for translation of a human genetic signature for the diagnosis of human radiation exposure and suggest the basis for further testing of CLPA as a candidate biodosimetric assay.

Novel Human Radiation Exposure Biomarker Panel Applicable for Population Triage

To identify a panel of radiation-responsive plasma proteins that could be used in a point-of-care biologic dosimeter to detect clinically significant levels of ionizing radiation exposure. Patients undergoing preparation for hematopoietic cell transplantation using radiation therapy (RT) with either total lymphoid irradiation or fractionated total body irradiation were eligible. Plasma was examined from patients with potentially confounding conditions and from normal individuals. Each plasma sample was analyzed for a panel of 17 proteins before RT was begun and at several time points after RT exposure. Paired and unpaired t tests between the dose and control groups were performed. Conditional inference trees were constructed based on panels of proteins to compare the non-RT group with the RT group. A total of 151 patients (62 RT, 41 infection, 48 trauma) were enrolled on the study, and the plasma from an additional 24 healthy control individuals was analyzed. In comparison with to control individuals, tenascin-C was upregulated and clusterin was downregulated in patients receiving RT. Salivary amylase was strongly radiation responsive, with upregulation in total body irradiation patients and slight downregulation in total lymphoid irradiation patients compared with control individuals. A panel consisting of these 3 proteins accurately distinguished between irradiated patients and healthy control individuals within 3 days after exposure: 97% accuracy, 0.5% false negative rate, 2% false positive rate. The accuracy was diminished when patients with trauma, infection, or both were included (accuracy, 74%-84%; false positive rate, 14%-33%, false negative rate: 8%-40%). A panel of 3 proteins accurately distinguishes unirradiated healthy donors from those exposed to RT (0.8-9.6 Gy) within 3 days of exposure. These findings have significant implications in terms of triaging individuals in the case of nuclear or other radiologic events.

A study of the energy absorption and exposure buildup factors of some anti-inflammatory drugs

Human radiation exposure is increasing due to radiation development in science and technology. The development of radioprotective agents is important for protecting patients from the side effects of radiotherapy and for protecting the public from unwanted irradiation. Radioprotective agents are used to reduce the damage caused by radiation in healthy tissues. There are several classes of radioprotective compounds that are under investigation. Analgesics and anti-inflammatory compounds are being considered for treating or preventing the effects of damage due to radiation exposure, or for increasing the chance of survival after exposure to a high dose of radiation. In this study, we investigated the radioprotective effects of some analgesic and anti-inflammatory compounds by evaluating buildup factors. The gamma ray energy absorption (EABF) and exposure buildup factors (EBF) were calculated to select compounds in a 0.015–15MeV energy region up to a penetration depth of 40mfp (mean free path). Variations of EABF and EBF with incident photon energy and penetration depth elements were also investigated. Significant variations in both EABF and EBF values were observed for several compounds at the moderate energy region. At energies below 0.15MeV, EABF and EBF values increased with decreasing equivalent atomic number (Zeq) of the samples. In addition, EABF and EBF were the largest for ibuprofen, aspirin, paracetamol, naproxen and ketoprofen at 0.05 and 0.06MeV, respectively, and the EABF value was 0.1MeV for aceclofenac. From these results, we concluded that the buildup of photons is less for aceclofenac compared to other materials.

Natural Radioactivity in Some Food Crops from Bangka-Belitung Islands, Indonesia

Natural radioactivities of food crops are the main sources of internal radiation exposure in humans. Bangka-Belitung islands of Indonesia has a higher natural background radioactivity than typical areas because of tin mining activities.The study was carried out to evaluate the natural radioactivity concentration in several food crops grown in Bangka and Belitung Islands. Food samples collected from Bangka and Belitung Islands were analyzed by means of a gamma spectroscopy for natural radionuclides 226 Ra, 232 Th and 40 K. The annual intake of the food was estimated on the basis of their average annual consumption. Calculations were also made to determine the effective dose to an individual consuming such diets. The intakes of these radionuclides were calculated using the concentrations in Bangka-Belitung foods and annual consumption rates of these food. Annual intakes of these radionuclides were as follows: 226 Ra = 190.00; 232 Th = 633.79 and 40 K = 2065.10 Bq/year. The annual internal dose resulting from ingestion of radionuclides in food was 0.205 mSv/year which is much lower than annual dose limit of 1 mSv for general public. The radionuclides with highest consumption is 40 K followed by 232 Th and 226 Ra. Received: 21 October 2013; Revised: 22 April 2014; Accepted: 28 April 2014

A single whole-body low dose X-irradiation does not affect L1, B1 and IAP repeat element DNA methylation longitudinally.

The low dose radioadaptive response has been shown to be protective against high doses of radiation as well as aging-induced genomic instability. We hypothesised that a single whole-body exposure of low dose radiation would induce a radioadaptive response thereby reducing or abrogating aging-related changes in repeat element DNA methylation in mice. Following sham or 10 mGy X-irradiation, serial peripheral blood sampling was performed and differences in Long Interspersed Nucleic Element 1 (L1), B1 and Intracisternal-A-Particle (IAP) repeat element methylation between samples were assessed using high resolution melt analysis of PCR amplicons. By 420 days post-irradiation, neither radiation- or aging-related changes in the methylation of peripheral blood, spleen or liver L1, B1 and IAP elements were observed. Analysis of the spleen and liver tissues of cohorts of untreated aging mice showed that the 17–19 month age group exhibited higher repeat element methylation than younger or older mice, with no overall decline in methylation detected with age. This is the first temporal analysis of the effect of low dose radiation on repeat element methylation in mouse peripheral blood and the first to examine the long term effect of this dose on repeat element methylation in a radiosensitive tissue (spleen) and a tissue fundamental to the aging process (liver). Our data indicate that the methylation of murine DNA repeat elements can fluctuate with age, but unlike human studies, do not demonstrate an overall aging-related decline. Furthermore, our results indicate that a low dose of ionising radiation does not induce detectable changes to murine repeat element DNA methylation in the tissues and at the time-points examined in this study. This radiation dose is relevant to human diagnostic radiation exposures and suggests that a dose of 10 mGy X-rays, unlike high dose radiation, does not cause significant short or long term changes to repeat element or global DNA methylation.

Radiation‐induced microRNA: Discovery, functional analysis, and cancer radiotherapy

MicroRNAs (miRNAs) are small non-protein coding RNA that play an important role in gene regulation. These RNA molecules function as post-transcriptional regulators. miRNAs bind to complementary sequences on target messenger RNA transcripts, usually resulting in translational repression or target mRNA degradation and gene silencing. miRNA are abundantly present in all human cells, target approximately 60% of all genes, and are able to repress hundreds of targets each. Since their discovery in 1993 miRNA are emerging as important modulators in cellular pathways such as growth and proliferation, apoptosis, carcinogenesis, timing of cell-fate decision, and metabolic pathways. A large number of studies have examined the general and specific effects of miRNAs perturbation in radiation-exposed cells. These studies include expression profiling of miRNA, functional analysis, the role of specific miRNAs in tumor radiosensitivity, and targeting miRNA for improved cancer radiotherapy. Other studies have explored the involvement of miRNA in radiobiological phenomenon like bystander effect. Emerging evidence is establishing that miRNA are involved in regulating radiation-induced cellular processes, can be exploited to improve cancer radiation therapy, and could serve as biomarkers of human radiation exposure.

The Cytokinesis-Block Micronucleus Assay on Peripheral Blood Lymphocytes as a Prospective Biological Test-System to Estimate the Influence of Radon on the Human Organism: Recent Progress and Future Prospects

This paper discusses the problem of assessing the negative after-effects of low doses of ionising radiation exposure in humans. Radon and its decay daughter products are the most widespread source of such irradiation. Miners (in both uranium and non-uranium mines) as well as laypeople in domestic life may be exposed to radon, making the problem of assessing the cytogenetic effects of exposure extremely crucial. One of the more promising test systems to assess the effect of radon is the cytokinesis-block micronucleus assay (CBMN) on peripheral blood lymphocytes, which has a number of advantages over other cytogenetic techniques. Recent progress and future prospects of this cytogenetic method are discussed here.

High LET (56)Fe ion irradiation induces tissue-specific changes in DNA methylation in the mouse.

DNA methylation is an epigenetic mechanism that drives phenotype and that can be altered by environmental exposures including radiation. The majority of human radiation exposures occur in a relatively low dose range; however, the biological response to low dose radiation is poorly understood. Based on previous observations, we hypothesized that in vivo changes in DNA methylation would be observed in mice following exposure to doses of high linear energy transfer (LET) (56) Fe ion radiation between 10 and 100 cGy. We evaluated the DNA methylation status of genes for which expression can be regulated by methylation and that play significant roles in radiation responses or carcinogenic processes including apoptosis, metastasis, cell cycle regulation, and DNA repair (DAPK1, EVL, 14.3.3, p16, MGMT, and IGFBP3). We also evaluated DNA methylation of repeat elements in the genome that are typically highly methylated. No changes in liver DNA methylation were observed. Although no change in DNA methylation was observed for the repeat elements in the lungs of these same mice, significant changes were observed for the genes of interest as a direct effect and a delayed effect of irradiation 1, 7, 30, and 120 days post exposure. At delayed times, differences in methylation profiles among genes were observed. DNA methylation profiles also significantly differed based on dose, with the lowest dose frequently affecting the largest change. The results of this study are the first to demonstrate in vivo high LET radiation-induced changes in DNA methylation that are tissue and locus specific, and dose and time dependent.

Novel Human Radiation Exposure Biomarker Panel Applicable for Patient Triage

Novel Human Radiation Exposure Biomarker Panel Applicable for Patient Triage

Bystander Signalling: Exploring Clinical Relevance Through New Approaches and New Models

Classical radiation biology research has centred on nuclear DNA as the main target of radiation-induced damage. Over the past two decades, this has been challenged by a significant amount of scientific evidence clearly showing radiation-induced cell signalling effects to have important roles in mediating overall radiobiological response. These effects, generally termed radiation-induced bystander effects (RIBEs) have challenged the traditional DNA targeted theory in radiation biology and highlighted an important role for cells not directly traversed by radiation. The multiplicity of experimental systems and exposure conditions in which RIBEs have been observed has hindered precise definitions of these effects. However, RIBEs have recently been classified for different relevant human radiation exposure scenarios in an attempt to clarify their role in vivo. Despite significant research efforts in this area, there is little direct evidence for their role in clinically relevant exposure scenarios. In this review, we explore the clinical relevance of RIBEs from classical experimental approaches through to novel models that have been used to further determine their potential implications in the clinic.

Evaluation of the Gamma-H2AX Assay for Radiation Biodosimetry in a Swine Model

There is a paucity of large animal models to study both the extent and the health risk of ionizing radiation exposure in humans. One promising candidate for such a model is the minipig. Here, we evaluate the minipig for its potential in γ-H2AX-based biodosimetry after exposure to ionizing radiation using both Cs137 and Co60 sources. γ-H2AX foci were enumerated in blood lymphocytes and normal fibroblasts of human and porcine origin after ex vivo γ-ray irradiation. DNA double-strand break repair kinetics in minipig blood lymphocytes and fibroblasts, based on the γ-H2AX assay, were similar to those observed in their human counterparts. To substantiate the similarity observed between the human and minipig we show that minipig fibroblast radiosensitivity was similar to that observed with human fibroblasts. Finally, a strong γ-H2AX induction was observed in blood lymphocytes following minipig total body irradiation. Significant responses were detected 3 days after 1.8 Gy and 1 week after 3.8 and 5 Gy with residual γ-H2AX foci proportional to the initial radiation doses. These findings show that the Gottingen minipig provides a useful in vivo model for validation of γ-H2AX biodosimetry for dose assessment in humans.

The Cellular and Molecular Carcinogenic Effects of Radon Exposure: A Review

Radon-222 is a naturally occurring radioactive gas that is responsible for approximately half of the human annual background radiation exposure globally. Chronic exposure to radon and its decay products is estimated to be the second leading cause of lung cancer behind smoking, and links to other forms of neoplasms have been postulated. Ionizing radiation emitted during the radioactive decay of radon and its progeny can induce a variety of cytogenetic effects that can be biologically damaging and result in an increased risk of carcinogenesis. Suggested effects produced as a result of alpha particle exposure from radon include mutations, chromosome aberrations, generation of reactive oxygen species, modification of the cell cycle, up or down regulation of cytokines and the increased production of proteins associated with cell-cycle regulation and carcinogenesis. A number of potential biomarkers of exposure, including translocations at codon 249 of TP53 in addition to HPRT mutations, have been suggested although, in conclusion, the evidence for such hotspots is insufficient. There is also substantial evidence of bystander effects, which may provide complications when calculating risk estimates as a result of exposure, particularly at low doses where cellular responses often appear to deviate from the linear, no-threshold hypothesis. At low doses, effects may also be dependent on cellular conditions as opposed to dose. The cellular and molecular carcinogenic effects of radon exposure have been observed to be both numerous and complex and the elevated chronic exposure of man may therefore pose a significant public health risk that may extend beyond the association with lung carcinogenesis.

The activity concentration of 210Po in Romanian commercial cigarettes and the radiation exposure estimation derived from their regular consumption

Due to the relatively high activity concentrations of (210)Po that are found in tobacco, cigarette smoking has been found to be the principal pathway of the intake of this radionuclide. The (210)Po concentrations in the lung tissues may contribute significantly to an increase in the internal radiation dose and in the number of instances of lung cancer observed among smokers. The study of (210)Po in tobacco is required due to its potential for human radiation exposure through ingestion and inhalation. The risk factor caused by (210)Po in Romanian commercial cigarettes is not yet evaluated. Ten of the most frequently smoked brands of cigarettes sold in Romania were investigated in this work for this purpose. The activity concentration of (210)Po was determined by alpha spectrometry using a PIPS detector after chemical leaching and spontaneous deposition of (210)Po on a stainless steel disc from diluted HCl solution. The samples were spiked with (209)Po for chemical recovery calculation. The (210)Po activity concentrations of the measured types of cigarettes ranged from 4.65 to 10.22 mBq sample(-1) and the resulted average concentration of (210)Po isotopes is 8.35±0.80 mBq cigarette(-1) (the errors form a 2σ interval of confidence). When comparing the results of this study with the activity concentration values reported by other countries it was found that the results of this study are in the lower end of the world range. The estimation of this study shows that cigarette smokers, who are smoking one pack (20 cigarettes) per day, are exposed to an effective dose of 75.51 μSv y(-1).

Severe pulmonary damages and high mortality rates shown in mice with combined burn and radiation injuries (P4005)

Abstract Non-clinical human radiation exposure events are often coupled with burns, and victims with combined injuries are extremely susceptible to sepsis stemming from various local infections, as compared with that of patients either exposed to burns or radiation alone. In patients with combined injuries, infectious complications result in a high mortality rate, and Pseudomonas aeruginosa is a pathogen frequently isolated from these patients. In this study, the severities of burn wound infections with P. aeruginosa were studied in mice with combined radiation and burn injuries (CI-mice). All of the CI-mice infected with 10 CFU/mouse of P. aeruginosa died within 2 days of the infection, while mice with either injury alone survived more than 4 weeks after the same infection. Five CFU/mouse of P. aeruginosa was shown to be 1 LD50 in CI-mice, while 3 - 9 x 103 CFU/mouse of the pathogen were required to kill all of the mice with either injury alone. Severe pulmonary inflammation and decreased alveolar spaces were specifically observed in CI-mice. Lineage−CD45+CD34+CD44+CD49b+ cells appeared in association with combined injuries inhibited bactericidal activities of alveolar macrophages isolated from normal mice. Lineage−CD45+CD34+CD44+CD49b+ cells may play a role on the high susceptibility of CI-mice to P. aeruginosa burn wound infection.

Ionizing radiation exposure and the development of intervertebral disc degeneration—no case to answer

In the following perspective article, Mellor and Breen provide a counterpoint to a previous perspective on the potential link between ionizing radiation exposure and intervertebral disc degeneration in humans [1]. The previous perspective asked, is this link a myth or reality? It suggested the potential for such a link. Mellor and Breen offer a drastically alternate view, in essence, that the question itself is flawed. To support their perspective, they explain the different units of radiation measurement and their conversion to risk in humans and how this impacts the previous perspective. They explain the variable sensitivity of different body tissues to radiation and highlight that neither human research nor any of the multiple international regulatory agencies have ever suggested that the intervertebral disc is sensitive to radiation. Finally, they claim that it is impossible to predict with any certainty the effects of low-level radiation on the intervertebral discs.

Gene expression as a biomarker for human radiation exposure

Accidental exposure to ionizing radiation can be unforeseen, rapid, and devastating. The detonation of a radiological device leading to such an exposure can be detrimental to the exposed population. The radiation-induced damage may manifest as acute effects that can be detected clinically or may be more subtle effects that can lead to long-term radiation-induced abnormalities. Accurate identification of the individuals exposed to radiation is challenging. The availability of a rapid and effective screening test that could be used as a biomarker of radiation exposure detection is mandatory. We tested the suitability of alterations in gene expression to serve as a biomarker of human radiation exposure. To develop a useful gene expression biomonitor, however, gene expression changes occurring in response to irradiation in vivo must be measured directly. Patients undergoing radiation therapy provide a suitable test population for this purpose. We examined the expression of CC3, MADH7, and SEC PRO in blood samples of these patients before and after radiotherapy to measure the in vivo response. The gene expression after ionizing radiation treatment varied among different patients, suggesting the complexity of the response. The expression of the SEC PRO gene was repressed in most of the patients. The MADH7 gene was found to be upregulated in most of the subjects and could serve as a molecular marker of radiation exposure.

山梨県産食品中の天然放射性核種（Pb-214, Bi-214）の濃度

The concentrations of Pb-214 and Bi-214 in groundwaters and agricultural products from several geologically distinct parts of the Yamanashi region of Japan were measured and compared. The concentrations of Pb-214 and Bi-214 in groundwaters were well correlated with each other, and were consistent with the predominant geology in each area. The concentrations of both radio-nuclides in agricultural products were much lower than the levels in groundwaters, and did not appear to be related to local geology or habitat. Freshwater fish showed higher levels than agricultural products, though the levels were lower than those in groundwaters. Unexpectedly, wild mushrooms (but not cultivated mushrooms) showed relatively high levels of Bi-214, though their levels of Pb-214 were undetectable. Based on the levels of Pb-214 and Bi-214 detected here, annual internal radiation exposure of humans from these sources is considered to be extremely low.