Biomarkers for human radiation exposure

There is a concern over the potential use of radioactive isotopes as a weapon of terror. The detonation of a radiation dispersal device, the so-called “dirty bomb” can lead to public panic. In order to estimate risks associated with radiation exposure, it is important to understand the biological effects of radiation exposure. Based on this knowledge, biomarkers to monitor potentially exposed populations after a radiological accident can be developed and would be extremely valuable for emergency response. While the traditional radiation exposure biomarkers based on cytogenetic assays serve as standard, the development of rapid and noninvasive tests for radiation exposure is needed. The genomics based knowledge is providing new avenues for investigation. The examination of gene expression after ionizing radiation exposure could serve as a potential molecular marker for biodosimetry. Microarray based studies are identifying new radiation responsive genes that could potentially be used as biomarkers of human exposure to radiation after an accident.     

Development of radioadaptive properties for microscopic fungi, long time located on terrains with a heightened background radiation after emergency on Chernobyl NPP

In 7 species of micromycetes which were isolated from radioactive contaminated areas of Chernobyl NPP zone under exposure of two artificial sources: y-low energy (121Sn) and radiation mix type gamma + beta (137Cs). Two new earlier unknown radioadaptive properties for fungi--radiotropism and radiostimulation were established. The strains, which were isolated from clean areas, did not have such features. All investigated strains, which have shown positive radiotropism at the same time, have shown stimulation of conidia germination and of length of the emergent hyphum under exposure to one of sources of radiation. It was shown that micro fungi having radioadaptive properties, the adaptive response to high (100-1000 Gy) ionizing radiation doses was found that is evidence of that these strains have high radio resistance level. Nevertheless fungal strains have shown varied response to presence of ionizing radiation depending on its type and absorbed dose.     

RADIATION: REGISTRATION OF SOURCES

Registration of sources of ionizing radiation, including x-ray machines and radioactive material used in the healing professions, is required by legislation recently enacted in California. Registration will provide information concerning the type and location of sources of radiation, and will provide a basis for the evaluation of a need for additional radiation control and protection measures in the future.As the medical uses of radiation procedures constitute a major portion of the total radiation exposure to the total population, it becomes increasingly important that physicians develop a reasonable and knowledgeable concept of not only the obvious benefits but also the actual and potential hazards of radiation as used in medicine. Practical and effective measures to minimize patient exposure, based on professional knowledge, competence and experience, with profession-wide participation and support, will insure the effective integration of the medical uses of radiation in the California Atomic Energy Development and Radiation Protection Program.     

hSnm1 colocalizes and physically associates with 53BP1 before and after DNA damage

snm1 mutants of Saccharomyces cerevisiae have been shown to be specifically sensitive to DNA interstrand crosslinking agents but not sensitive to monofunctional alkylating agents, UV, or ionizing radiation. Five homologs of SNM1 have been identified in the mammalian genome and are termed SNM1, SNM1B, Artemis, ELAC2, and CPSF73. To explore the functional role of human Snm1 in response to DNA damage, we characterized the cellular distribution and dynamics of human Snm1 before and after exposure to DNA-damaging agents. Human Snm1 was found to localize to the cell nucleus in three distinct patterns. A particular cell showed diffuse nuclear staining, multiple nuclear foci, or one or two larger bodies confined to the nucleus. Upon exposure to ionizing radiation or an interstrand crosslinking agent, the number of cells exhibiting Snm1 bodies was reduced, while the population of cells with foci increased dramatically. Indirect immunofluorescence studies also indicated that the human Snm1 protein colocalized with 53BP1 before and after exposure to ionizing radiation, and a physical interaction was confirmed by coimmunoprecipitation assays. Furthermore, human Snm1 foci formed after ionizing radiation were largely coincident with foci formed by human Mre11 and to a lesser extent with those formed by BRCA1, but not with those formed by human Rad51. Finally, we mapped a region of human Snm1 of approximately 220 amino acids that was sufficient for focus formation when attached to a nuclear localization signal. Our results indicate a novel function for human Snm1 in the cellular response to double-strand breaks formed by ionizing radiation.     

The dose estimation of woody plants in the long-term after the Chernobyl NPP accident

Dosimetric models have been developed to estimate the exposure doses of woody plants growing in the area contaminated by long-lived radionuclides. The models are parameterized based on the data obtained from the experimental plots in the south-west districts of the Bryansk region affected by radioactive fallout of the Chernobyl NPP accident. Doses are estimated to generative organs of pine trees from these plots. The contribution from various sources and types of ionizing radiation to the absorbed dose formation for these objects is determined.     

Mortality from solid cancers other than lung,liver, and bone in relation to external dose among plutonium and non-plutonium workers in the Mayak Worker Cohort

Exposure to ionizing radiation has well-documented long-term effects on cancer rates and other health outcomes in humans. While in vitro experimental studies had demonstrated that the nature of some radiation effects depend on both total dose of the radiation and the dose rate (i.e., the pattern of dose distribution over time), the question of whether or not the carcinogenic effect of radiation exposure depends on the dose rate remains unanswered. Another issue of interest concerns whether or not concomitant exposure to external gamma rays and inhaled plutonium aerosols has any effect on the external exposure effects. The analyses of the present paper focus on the risk of solid cancers at sites other than lung, liver, and bone in Mayak workers. Recent findings are reviewed indicating that there is no evidence of plutonium dose response for these cancers in the Mayak worker cohort. Then the evidence for differences in the external dose effects among workers with and without the potential for exposure to alpha particles from inhaled plutonium is examined. It is found that there is no evidence that exposure to plutonium aerosols significantly affects the risk associated with external exposure. While the Mayak external dose risk estimate of an excess relative risk of 0.16 per Gy is somewhat lower than an appropriately normalized risk estimate from the Life Span Study of Japanese atomic bomb survivors, the uncertainties in these estimates preclude concluding that the external dose excess relative risks of this group of solid cancers differ in the two cohorts.     

Microsatellite mutations in the offspring of irradiated parents 19 years after the Cesium-137 accident

In September of 1987, a radiotherapy unit containing 50.9 TBq of Cs(137)Cl was removed from an abandoned radiotherapy clinic. This unit was subsequently disassembled leading to the most serious radiological accident yet to occur in the Western hemisphere. This event provides an opportunity to assess the genetic effects of ionizing radiation. We surveyed genetic variation of 12 microsatellite loci in 10 families of exposed individuals and their offspring and also in non-exposed families from the same area of Goias state. We found an increase in the number of new alleles in the offspring of the exposed individuals. The mutation rate was found to be higher in the exposed families compared to the control group. These results indicated that exposure to ionizing radiation can be detected in offspring of exposed individuals and also suggest that the elevated microsatellite mutation rate can be attributed to radioactive exposure.     

Microsatellite mutations in the offspring of irradiated parents 19 years after the Cesium-137 accident

In September of 1987, a radiotherapy unit containing 50.9 TBq of Cs¹³⁷Cl was removed from an abandoned radiotherapy clinic. This unit was subsequently disassembled leading to the most serious radiological accident yet to occur in the Western hemisphere. This event provides an opportunity to assess the genetic effects of ionizing radiation. We surveyed genetic variation of 12 microsatellite loci in 10 families of exposed individuals and their offspring and also in non-exposed families from the same area of Goias state. We found an increase in the number of new alleles in the offspring of the exposed individuals. The mutation rate was found to be higher in the exposed families compared to the control group. These results indicated that exposure to ionizing radiation can be detected in offspring of exposed individuals and also suggest that the elevated microsatellite mutation rate can be attributed to radioactive exposure.     

Influence of low dozes of ionizing radiation on accumulation of melanin pigments and catalase and superoxidedismutase activities in Cladosporium cladosporioides

Influence of low dozes of ionizing radiation on melanin pigments synthesis and activity of antioxidant enzymes catalase and superoxidedismutase of two strains of Cladosporium cladosporioides 4, (isolated from radioactive soil) and 396 (control) were investigated. It was shown, that in C. cladosporioides 4 under the exposure of ionizing radiation an increase of melanin synthesis in a stationary growth phase and increase of superoxidedismutase activity in a logarithmic phase were observed; in the control strain C. cladosporioides 396 activation of melanin synthesis and superoxide dismutase activity in both growth phases was revealed. It was established that in C. cladosporioides 4 the endocellular catalase activity in a logarithmic phase is 3.2 times higher, than in control strain. Under the action of ionizing radiation a 2-fold increase of this enzyme activity unlike the control strain in which the activity inhibition was revealed. The obtained results testify to the complex response of antioxidant systems and melanin to the action of low dozes of radiation which depends on the growth phase and presence of radioadaptation properties in the investigated fungi.     

The role of regulatory networks of the cell response to damages in radiation effects

In view of modern knowledge and concepts about components, function and mechanisms of response of cell molecular structures to damaging effects, response which is generating specialized modules of reactions, it is shown that main components of the mechanism of maintenance of genome constancy at ionizing radiation exposure are checkpoints of cell cycle, DNA repair and apoptosis. They operate under the control of a genetic system at participation of Tp53 gene, corresponding protein and of regulatory networks formed by cascades of mitogen-activated protein kinases (MAPK). At ionizing radiation exposure the MAPK special modules participate in formation of radiation effect: ERK 1/2 (extracellular signal-regulated kinase 1 and 2), JNK/SAPK (c-Jun N-terminal kinase/stress activated protein kinase) and p38 MAPK. Executing physiological functions of maintenance of normal life activity of cells, they do not lose this capacity after exposure to ionizing radiation, participating in formation of radiation effect in a wide range of doses, and are inactivated only by exposure to very high doses. It is concluded that in light of the modern data the main problem is not a problem of mechanisms of biological effect of ionizing radiation but a problem of biological mechanisms of radiation exposure.     

Mutation induction by inhaled radon progeny modeled at the tissue level

The observable responses of living systems to ionizing radiation depend on the level of biological organization studied. Understanding the relationships between the responses characteristic of the different levels of organization is of crucial importance. The main objective of the present study is to investigate how some cellular effects of radiation manifest at the tissue level by modeling mutation induction due to chronic exposure to inhaled radon progeny. For this purpose, a mathematical model of the bronchial epithelium was elaborated to quantify cell nucleus hits and cell doses. Mutagenesis was modeled considering endogenous as well as radiation-induced DNA damages and cell cycle shortening due to cell inactivation. The model parameters describing the cellular effects of radiation are obtained from experimental data. Cell nucleus hits, cell doses, and mutation induction were computed for the activity hot spots of the large bronchi at different exposures. Results demonstrate that the mutagenic effect of densely ionizing radiation is dominated by cell cycle shortening due to cell inactivation and not by DNA damages. This suggests that radiation burdens of non-progenitor cells play a significant role in mutagenesis in case of protracted exposures to densely ionizing radiation. Mutation rate as a function of dose rate exhibits a convex shape below a threshold. This threshold indicates the exhaustion of the tissue regeneration capacity of local progenitor cells. It is suggested that progenitor cell hyperplasia occurs beyond the threshold dose rate, giving a possible explanation of the inverse dose-rate effect observed in the epidemiology of lung cancer among uranium miners.     

Synergistic effects of ionizing radiation and 60 Hz magnetic fields

Experiments designed to evaluate the synergistic production of clastogenic effects by ionizing radiation and 60 Hz magnetic fields were performed using human lymphocytes from peripheral blood. Following exposure to ionizing radiation, cells were cultured in 60 Hz magnetic fields having field strengths up to 1.4 mT. Cells exposed to both ionizing radiation and 60 Hz magnetic fields demonstrated an enhanced frequency of near tetraploid chromosome complements, a feature not observed following exposure to only ionizing radiation. The results are discussed in the context of a multiple-stage model of cellular transformation, employing both initiating and promoting agents. © 1993 Wiley-Liss. Inc.     

Increased oxidative stress in barn swallows from the Chernobyl region

The Chernobyl nuclear accident produced the largest unintended release of radionuclides in history, with dramatic consequences for humans and other organisms. Exposure to ionizing radiation is known to reduce circulating and stored levels of specific antioxidants in birds and humans, thus potentially increasing oxidative stress. However, overall effects of radioactive exposure on oxidative status have never been investigated in any free ranging vertebrate. We measured plasma antioxidant capacity and concentration of reactive oxygen metabolites in adult barn swallows (Hirundo rustica) from colonies with variable background radiation levels in the Chernobyl region in Ukraine and Belarus. We predicted that antioxidants would decrease while reactive oxygen metabolites would increase with exposure to increasing levels of radiation at the breeding sites. Consistent with this expectation, radiation level positively predicted plasma concentration of reactive oxygen metabolites, whereas no significant covariation was found with non-enzymatic plasma antioxidant capacity. An index of oxidative stress was also larger in barn swallows exposed to high contamination levels. Thus, radioactive contamination appeared to be responsible for the increased generation of reactive oxygen metabolites and the imbalance between reactive oxygen metabolites and non-enzymatic plasma antioxidant capacity.     

Radioactivity and radiation safety: basic concepts for laboratory animal technologists and technicians

Laboratory animals treated with radioactive compounds are a radiation-safety concern. It is important for technologists and technicians who work with these animals to understand ionizing radiation and radiation-safety practices. The author discusses licensing, contamination control, and how to deal with radioactive waste.     

Altitude, radiation, and mortality from cancer and heart disease

The variation in background radiation levels is an important source of information for estimating human risks associated with low-level exposure to ionizing radiation. Several studies conducted in the United States, correlating mortality rates for cancer with estimated background radiation levels, found an unexpected inverse relationship. Such results have been interpreted as suggesting that low levels of ionizing radiation may actually confer some benefit. An environmental factor strongly correlated with background radiation is altitude. Since there are important physiological adaptations associated with breathing thinner air, such changes may themselves influence risk. We therefore fit models that simultaneously incorporated altitude and background radiation as predictors of mortality. The negative correlations with background radiation seen for mortality from arteriosclerotic heart disease and cancers of the lung, the intestine, and the breast disappeared or became positive once altitude was included in the models. By contrast, the significant negative correlations with altitude persisted with adjustment for radiation. Interpretation of these results is problematic, but recent evidence implicating reactive forms of oxygen in carcinogenesis and atherosclerosis may be relevant. We conclude that the cancer correlational studies carried out in the United States using vital statistics data do not in themselves demonstrate a lack of carcinogenic effect of low radiation levels, and that reduced oxygen pressure of inspired air may be protective against certain causes of death.     

The biological effects of diagnostic cardiac imaging on chronically exposed physicians: the importance of being non-ionizing

Ultrasounds and ionizing radiation are extensively used for diagnostic applications in the cardiology clinical practice. This paper reviewed the available information on occupational risk of the cardiologists who perform, every day, cardiac imaging procedures. At the moment, there are no consistent evidence that exposure to medical ultrasound is capable of inducing genetic effects, and representing a serious health hazard for clinical staff. In contrast, exposure to ionizing radiation may result in adverse health effect on clinical cardiologists. Although the current risk estimates are clouded by approximations and extrapolations, most data from cytogenetic studies have reported a detrimental effect on somatic DNA of professionally exposed personnel to chronic low doses of ionizing radiation. Since interventional cardiologists and electro-physiologists have the highest radiation exposure among health professionals, a major awareness is crucial for improving occupational protection. Furthermore, the use of a biological dosimeter could be a reliable tool for the risk quantification on an individual basis.     

Radiation Protection in Canada: Part VII. The Role of Industrial Hygiene in the Field of Radiation Protection

The main emphasis of a provincial radiation protection program is on ionizing radiation produced by machines, although assistance is given to the Federal Radiation Protection Division in its program relating to radioactive substances. The basis for the Saskatchewan program of radiation protection is the Radiological Health Act 1961. An important provision of the Act is annual registration of radiation equipment. The design of the registration form encourages a “do-it-yourself” radiation and electrical safety inspection.Installations are inspected every two years by a radiation health officer. Two hundred and twenty-one deficiencies were found during inspection of 224 items of radiation equipment, the commonest being failure to use personal film badges. Insufficient filtration of the beam, inadequate limitation of the beam, and unnecessary exposure of operators were other common faults.Physicians have a responsibility to weigh the potential advantages against the hazards when requesting radiographic or fluoroscopic procedures.     

A sense of danger from radiation

Tissue damage caused by exposure to pathogens, chemicals and physical agents such as ionizing radiation triggers production of generic "danger" signals that mobilize the innate and acquired immune system to deal with the intrusion and effect tissue repair with the goal of maintaining the integrity of the tissue and the body. Ionizing radiation appears to do the same, but less is known about the role of "danger" signals in tissue responses to this agent. This review deals with the nature of putative "danger" signals that may be generated by exposure to ionizing radiation and their significance. There are a number of potential consequences of "danger" signaling in response to radiation exposure. "Danger" signals could mediate the pathogenesis of, or recovery from, radiation damage. They could alter intrinsic cellular radiosensitivity or initiate radioadaptive responses to subsequent exposure. They may spread outside the locally damaged site and mediate bystander or "out-of-field" radiation effects. Finally, an important aspect of classical "danger" signals is that they link initial nonspecific immune responses in a pathological site to the development of specific adaptive immunity. Interestingly, in the case of radiation, there is little evidence that "danger" signals efficiently translate radiation-induced tumor cell death into the generation of tumor-specific immunity or normal tissue damage into autoimmunity. The suggestion is that radiation-induced "danger" signals may be inadequate in this respect or that radiation interferes with the generation of specific immunity. There are many issues that need to be resolved regarding "danger" signaling after exposure to ionizing radiation. Evidence of their importance is, in some areas, scant, but the issues are worthy of consideration, if for no other reason than that manipulation of these pathways has the potential to improve the therapeutic benefit of radiation therapy. This article focuses on how normal tissues and tumors sense and respond to danger from ionizing radiation, on the nature of the signals that are sent, and on the impact on the eventual consequences of exposure.     

Genomic damage in children accidentally exposed to ionizing radiation: a review of the literature

During the last decade, our knowledge of the mechanisms by which children respond to exposures to physical and chemical agents present in the environment, has significantly increased. Results of recent projects and programmes focused on children's health underline a specific vulnerability of children to environmental genotoxicants. Environmental research on children predominantly investigates the health effects of air pollution while effects from radiation exposure deserve more attention. The main sources of knowledge on genome damage of children exposed to radiation are studies performed after the Chernobyl nuclear plant accident in 1986. The present review presents and discusses data collected from papers analyzing genome damage in children environmentally exposed to ionizing radiation. Overall, the evidence from the studies conducted following the Chernobyl accident, nuclear tests, environmental radiation pollution and indoor accidental contamination reveals consistently increased chromosome aberration and micronuclei frequency in exposed than in referent children. Future research in this area should be focused on studies providing information on: (a) effects on children caused by low doses of radiation; (b) effects on children from combined exposure to low doses of radiation and chemical agents from food, water and air; and (c) specific effects from exposure during early childhood (radioisotopes from water, radon in homes). Special consideration should also be given to a possible impact of a radiochemical environment to the development of an adaptive response for genomic damage. Interactive databases should be developed to provide integration of cytogenetic data, childhood cancer registry data and information on environmental contamination. The overall aim is to introduce timely and efficient preventive measures, by means of a better knowledge of the early and delayed health effects in children resulting from radiation exposure.