Low-dose ionizing radiation and chromosome translocations: a review of the major considerations for human biological dosimetry

Chromosome translocations are a molecular signature of ionizing radiation exposure. Translocations persist significantly longer after exposure than other types of chromosome exchanges such as dicentrics. This persistence makes translocations the preferred aberration type for performing radiation dosimetry under conditions of protracted exposure or when exposure assessments are temporally delayed. Low doses of radiation are inherently difficult to quantify because the frequency of induced events is low and the background level of translocations among unexposed subjects can show considerable variability. Analyses of translocation frequencies can be confounded by several factors, including age of the subject, lifestyle choices such as cigarette smoking, the presence of clones of abnormal cells, and possibly genotypic variability among subjects. No significant effects of gender or race have been observed, but racial differences have not been completely ruled out. Translocation analyses may be complicated by the presence of different types of exchanges, i.e., reciprocal or non-reciprocal, and because translocations sometimes occur as a component of complex exchanges that include other forms of chromosome rearrangements. Rates of radiation exposure, ranging from acute to chronic, are known to influence the accumulation of translocations and may also affect their persistence. The influences on translocation frequencies of low-dose radiation hypersensitivity as well as the bystander effect and the adaptive response remain poorly characterized. Thus, quantifying the relationship between radiation dose and the frequency of translocations in any given subject requires attention to multiple issues. Part of the solution to understanding the in vivo dose-response relationship is to have accurate estimates of the baseline levels of translocations in healthy unexposed subjects, and some work in this area has been accomplished. Long-term cytogenetic follow-up of exposed subjects is needed to characterize translocation persistence, which is especially relevant for risk analyses. More work also needs to be done in the area of quantifying the role of known confounders. Characterizing the role of genotype will be especially important. Improvements in the ability to use translocation frequencies for low-dose biological dosimetry will require scoring very large numbers of cells per subject, which may be accomplished by developing a rapid automated image analysis system. This work would enhance our comprehension of the effects of low-dose radiation exposure and could lead to significant improvements in understanding the relationship between chromosome damage and human health.     

KCl:Dy phosphor for thermoluminescence dosimetry of ionizing radiation

The thermoluminescence (TL) characterizations of γ‐irradiated KCl:Dy phosphor for radiation dosimetry are reported. All phosphors were synthesized via a wet chemical route. Minimum fading of TL intensity is recorded in the prepared material. TL in samples containing different concentrations of Dy impurity was studied at different γ‐irradiation doses. Peak TL intensities varied sublinearly with γ‐ray dose in all samples, but were linear between 0.08 to 0.75 kGy for the KCl:Dy (0.1 mol%) sample. This material may be useful for dosimetry within this range of γ‐ray dose. TL peak height was found to be dependant on the concentration (0.05–0.5 mol%) of added Dy in the host. Copyright © 2012 John Wiley & Sons, Ltd.     

Immunochemical determination of DNA damage induced by high doses of ionizing radiation

It was shown by the immunochemical method that DNA of X-irradiated E. coli cells of a radiosensitive mutant ABA88uvr A6 can react with the antiserum to thymine dimers which, in all appearance, are induced by ionizing radiation in bacterial DNA. The number of thymine dimers in DNA of E. coli AB1886uvr A6 increased with the dose increase. No dimers were detected in radioresistant cells of M. radioproteolyticus probably due to the effective excision thereof.     

Effect of ionizing radiation at high doses on the cyclic nucleotide content of the rat brain

The study of the rat brain after irradiation with superlethal doses of 100 and 500 Gy has revealed a decrease in the cAMP content at early times after exposure. The most considerable decline in the cGMP content was noted in the cerebellum and cerebral hemisphere cortex where low cGMP level was retained for 24 h following irradiation. It is suggested that the observed changes play an important role in the development of the CNS syndrome.     

Chromosome aberration analysis and the influence of mitotic delay after simulated partial-body exposure with high doses of sparsely and densely ionising radiation

The influence of high doses of sparsely and densely ionising radiation on the yield of aberrant human peripheral lymphocytes in simulated partial-body exposures was studied by investigating radiation-induced chromosome aberration frequencies, namely dicentric and centric ring chromosomes. Peripheral blood samples from two volunteers were irradiated with high doses of 200 kV X-rays or neutrons with a mean energy of <E _n>=2.1 MeV and partial-body exposure was simulated by mixing irradiated and non-irradiated blood from the same two donors in proportions of 25, 50, and 75%. Lymphocytes were cultured and first-division metaphase cells were collected after culture times of 48, 56, and 72 h. A significant underrepresentation of dicentric and centric ring chromosomes was observed at the three highest doses of X-rays between the different culture times for nearly all proportions. After neutron irradiation, some significant differences were observed at all doses and all culture times, without however, revealing any systematic pattern. The distribution of dicentric and ring chromosomes showed overdispersion for both radiation types. After simulated partial-body exposures with 200 kV X-rays and <E _n>=2.1 MeV neutrons, strong mitotic delays could be observed, which depended on both the irradiated volume and the applied dose: the smaller the irradiated volume and the higher the dose, the higher was the selective advantage of non-irradiated cells. For the purpose of biological dosimetry after partial body exposure, an extension of the lymphocyte culture time is suggested at least for doses ≥3.0 Gy of 200 kV X-rays and ≥0.5 Gy of <E _n>=2.1 MeV neutrons in order to prevent a systematic underestimation of cytogenetic damage.     

Influence of low doses of ionizing radiation on tenascin expression in hybridoma cell systems

One of the achievements of the modern radiation ecology is the preparation and application of stable eukariotic cell lines to solve various problems occurring under exposure to ionizing radiation, especially to low doses. The detection of onco-fetal protein--tenascin in different embryonic and tumor cells of humans and animals supposes the probability of appropriate gene expression in lymphoid cells, including hybridomal cells. Using the immunochemical method, the study of tenascin expression in two mouse hybridomal lines was carried out. Tenascin was revealed in hybridomal lines MLC-1 and K-48. Further hybridomal cell lines were exposed to X-ray radiation (120 KV) with doses 2.10,15 cGy. The obtained results demonstrated the sensitivity of tenascin expression to low doses of ionizing radiation, that may be used as a convenient model of studying of genotoxic effects of various damaging ionizing agents on a cell level.     

Effect of graded doses of ionizing radiation on the human testis

A portable unit was developed to provide uniform irradiation of the human testes. The device had built-in radiological protection and provided a dosage independent of the subject geometry, uniform to within +or- 5%. Single doses, between 8-600 rad were administered to the testes of human subjects. Observations were made both before and following irradiation. Parameters evaluated included sperm concentration, motility and morphology, seminal fluid volume, plasma and urinary gonadotropin and testosterone levels, urinary estrogens, and comparison of testicular biopsies taken before and after irradiation in the same subject. Dose-response relationships and recovery times were determined for each dose range studied.     

The regulation of pollen tube growth in Douglas-fir following high doses of ionizing radiation

The relationship between temperature and sensitivity to gibberellin A₃ (GA₃) was studied in lettuce seedlings (Lactuca sativa L. cv. Arctic). Dose/response curves for hypocotyl elongation (10^-4 mol l^-1 to 10^-8 mol l^-1) were constructed for a range of temperatures and the slope of the linear portion of the plots used as an indication of the sensitivity to GA₃. Hypocotyls were unresponsive to GA₃ below 13°C but above this temperature sensitivity increased linearly. Plots of growth rate against temperature had inflexions between 12°C and 13°C, with slopes above this point which increased with increasing GA₃ concentration. The Q₁₀ value for response increased in a similar manner. Reaction rates of NAD-dependent malate dehydrogenase and peroxidase extracted from hypocotyls varied linearly with temperature whilst nonspecific tetrazolium reduction, a membrane based activity, showed an abrupt rate change above 14°C. Pre-exposure to GA₃ had no effect on the temperature responses of soluble or particulate enzymes.Abbreviation GA₃ gibberellin A₃     

Influence of very low doses of ionizing radiation on Synechococcus lividus metabolism during the initial growth phase

Previous results from this laboratory have shown that very low chronic doses of gamma radiation can stimulate proliferation of the Cyanobacterium Synechococcus lividus. This modification of cell proliferation occurred during the first doubling. In this paper, we have compared the metabolism of cells cultivated in a normal environment or under chronic irradiation. Incubation of the cells in a new medium induced a high superoxide dismutase (EC 1.15.1.1, SOD) activity at the 18th hour and a degradation of phycocyanin, thus demonstrating that cells were submitted to a photooxidative stress. This increase in superoxide dismutase activity was followed by concomittant peaks of glutathione reductase (EC 1.6.4.2, GR) and glucose-6-phosphate dehydrogenase (EC 1.1.1.49, G6P-DH) at the 24th hour. Irradiated cultures at a dose of 53.5 mGray/year show an earlier and higher peak of SOD, GR, and G6P-DH. In a second stage, cultures showed an earlier onset of photosynthesis under irradiation, as evidenced by an increase in pigment content and an enhancement of glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.13, GAP-DH). These results show that the radiostimulation is related to the activation of enzymes protecting against peroxides that were induced under oxidative circumstances and to the activation of a glucose catabolism via the oxidative pentose phosphate pathway.Abbreviations mGy milli-Gray - SOD superoxide dismutase - G6P-DH glucose-6-phosphate dehydrogenase - GAP-DH glycer-aldehyde-3-phosphate dehydrogenase - GSSG oxidized glutathione     

Use of chemical dosimetry for comparison of ultrasound and ionizing radiation effects on cavitation

A comparison of the effects of ultrasound produced by low- and high-frequency ultrasonic apparatuses upon biological systems is one of the basic problems when studying ultrasound cavitation effects. One possibility for how to compare these effects is the indirect method which uses well-known physical quantities characterizing the interaction of ionizing radiation with matter and which also converts these quantities to one common physical quantity. The comparison was performed with two methods applied to the chemical dosimetry of ionizing radiation. The first method employed a two-component dosimeter which is composed of 50 % chloroform and 50 % re-distilled water (i.e. Taplin dosimeter). The other method used a modified iodide dosimeter prepared from a 0.5 M potassium iodide solution. After irradiation or ultrasound exposure, measurable chemical changes occurred in both dosimeters. The longer the exposure, the greater the chemical changes. These effects are described by the relationship of these changes versus the exposure times in both dosimeters. The UZD 21 ultrasonic disintegrator (with a frequency of 20 kHz, 50 % power output) was used as a low-frequency ultrasound source, and the BTL-07 therapeutic instrument (with a frequency of 1 MHz and intensity of 2 W/cm2) was used as a high-frequency cavitation ultrasound source. For comparison, a 60 Co gamma source was applied (60 Co, gamma energies of 1.17 and 1.33 MeV, activity of 14 PBq). Results of this study have demonstrated that the sonochemical products are generated during exposure in the exposed samples of both dosimeters for all apparatuses used. The amount of these products depends linearly upon the exposure time. The resulting cavitation effects were recalculated to a gray-equivalent dose (the proposed unit is cavitation gray [cavitGy]) based on the sonochemical effects compared to the effects of ionizing radiation from the 60 Co source.     

Characteristic cytogenetic effects of small doses of ionizing radiation

A study was made of the frequency of chromosome aberrations in human lymphocyte culture after gamma-irradiation (60Co) with doses ranging from 0.05 to 1.0 Gy at dose--rates of 0,005, 0.05 and 0.5 Gy/min. The frequency of structural changes in chromosomes at low doses was higher than it was expected in the case of extrapolating the effect produced by high to low doses of radiation; within the dose range from 0.1 to 0.5 Gy a plateau was registered for aberrations of the exchange type (dicentrics and rings). The abnormal character of the dose dependence of the yield of chromosome aberrations persisted with all three dose - rates under study.     

Brain beta-adrenergic and GABA-ergic receptors in rats after exposure to high doses of ionizing radiation

The radioactive ligands, [3H]dihydroalprenolol and [3H]muscimol, were used to estimate the condition of beta-adrenoreceptors of the brain cortex and GABA-receptors of the cerebellum during transient neurologic disorders caused by irradiation of rats with high-energy (20 MeV) electrons of 200 Gy. No significant changes were observed in the GABA-ergic brain system while the changes in beta-adrenoreceptors of the brain were pronounced and manifested by the loss by the receptors of their ability to bind the specific ligand, dihydroalprenolol. The changes observed were reversible and correlated with the development of neurologic disorders.     

Pseudonormal thymocytes--a unique reaction of the lymphoid elements of the thymic cortex to high doses of ionizing radiation

The method of electron microscopy was used to study the phenomenon of "paradoxical resistance" of thymocytes to very high radiation doses (40 and 200 Gy). The formation of "pseudonormal" thymocytes, which represented a peculiar form of radiation death of these cells, was shown to be a function of radiation dose and time after irradiation.     

The micronucleus assay as a biological dosimeter in hospital workers exposed to low doses of ionizing radiation

The health risk associated with low levels of ionizing radiation is still a matter of debate. A number of factors, such as non-target effects, adaptive responses and low-dose hypersensitivity, affect the long-term outcome of low-dose exposures. Cytogenetic bio-dosimetry provides a measure of the absorbed dose, taking into account the individual radiation sensitivity. The aim of the present study is to evaluate the value of the micronucleus (MN) test as a bio-dosimeter in hospital workers exposed to low doses of ionizing radiation. Blood samples were obtained from 30 subjects selected among workers exposed to X- and gamma-radiation, and 30 controls matched for sex, age and smoking from the same hospital. Micronucleus frequencies were analyzed by use of the cytokinesis-block method. The MN frequency was compared among the groups considering the confounding factors and the length of employment. No increase in the number of bi-nucleated cells with MN (BNMN), but a significant increase in the number of mono-nucleated cells with micronuclei (MOMN) was observed in exposed subjects compared with the controls. The relationship between MN frequency and accumulated dose (mSv) was evaluated. The length of employment did not affect the extent of MN frequency, but an increase of BNMN and MOMN cells was observed based on the accumulated radiation dose. Our study shows the sensitivity of the MN test in the detection of cytogenetic effects of cumulative exposure levels, suggesting the potential usefulness of this assay in providing a biological index in medical surveillance programs.     

The central regulation of pain sensitivity in rats after irradiation with high doses of ionizing radiation

It was shown that during 24 h following whole-body exposure of male rats to gamma-quanta (150 Gy) the latent period of their response to the thermal effect increased a "tail-flick" test) and the threshold of the nociceptive response to an electric stimulus (the vocalization threshold) decreased. A correlation was found between the initial response to the nociceptive effects and variation of these values in irradiated animals.