Bystander and delayed effects after fractionated radiation exposure

Human immortalized keratinocytes were exposed to a range of single or fractionated doses of gamma rays from (60)Co, to medium harvested from donor cells exposed to these protocols, or to a combination of radiation and irradiated cell conditioned medium (ICCM). The surviving fractions after direct irradiation or exposure to ICCM were determined using a clonogenic assay. The results show that medium harvested from cultures receiving fractionated irradiation gave lower "recovery factors" than direct fractionated irradiation, where normal split-dose recovery occurred. The recovery factor is defined here as the surviving fraction of the cells receiving two doses (direct or ICCM) separated by an interval of 2 h divided by the surviving fraction of cells receiving the same dose in one exposure. After treatment with ICCM, the recovery factors were less than 1 over a range of total doses from 5 mGy-5 Gy. Varying the time between doses from 10 min to 180 min did not alter the effect of ICCM, suggesting that two exposures to ICCM are more toxic than one irrespective of the dose used to generate the response. In certain protocols using mixtures of direct irradiation and ICCM, it was possible to eliminate the bystander effect. If bystander factors are produced in vivo, then they may reduce the sparing effect of the dose fractionation.     

Genetic effect of 3-carbethoxypsoralen, angelicin, psoralen and 8-methoxypsoralen plus 365-nm irradiation in Saccharomyces cerevisiae: induction of reversions, mitotic crossing-over, gene conversion and cytoplasmic "petite" mutations.

The genetic effects of two mono-functional photosensitizing furocoumarins, 3-carbethoxypsoralen (3-CPs) and angelicin, were compared with those of two bi-functional furocoumarins, 8-methoxypsoralen and psoralen in Saccharomyces cerevisiae. A drug concentration of 5 X 10(-5) M plus various doses of 365-nm irradiation at a dose rate of 1.2 kJ m-2 min-1 were used. Per dose of 365-nm irradiation, the frequency of induced nuclear events such as gene mutation and mitotic recombination (conversion and crossing-over) is higher for the bi-functional than for the mono-functional compounds. The higher efficiency of the bi-functional furocoumarins is also evident when the frequency of mutants is expressed as a function of survival. However, the photo-addition of the 4 furocoumarins studied leads to the same response for the induction of recombinational events per viable cell. Amongst genetically altered colonies induced in the diploid strains D5 and D7, the colonies corresponding to the induction of crossing-over are effectively produced by bi-functional furocoumarins, but are rare (D7) or even absent (D5) after treatment with monofunctional furocoumarins. This suggests a certain specificity of genetic alterations produced by the bi-functional agents. 3-CPs is the most effective inducer on the cytoplasmic "petite" mutation in stationary phase cells per unit irradiation dose or per viable cell.     

Highly viscous polysaccharide produced by an Enterobacter isolate on a hemicellulose hydrolysate

Summary A new anionic extracellular polysaccharide (AEPS) with high molecular mass (1700 kD) was produced by an isolate tentatively identified as Enterobacter cloacae isolated from an acid hydrolysate of wood. The sugar composition of this AEPS is glucose, galactose, glucuronic acid, and fucose (5:4:4:11). Under specified conditions this AEPS is rheologically comparable to xanthan.     

The effectiveness of 20 mev protons at nanosecond pulse lengths in producing chromosome aberrations in human-hamster hybrid cells

Laser accelerated radiotherapy is a potential cancer treatment with proton and carbon-ion beams that is currently under development. Ultra-fast high-energy laser pulses will accelerate ion beams that deliver their dose to a patient in a "pulsed mode" that is expected to differ from conventional irradiation by increasing the dose delivery rate to a tissue voxel by approximately 8 orders of magnitude. In two independently performed experiments at the ion microprobe SNAKE of the 14 MV Munich tandem accelerator, A(L) cells were exposed either to protons with 1-ns pulse durations or to protons applied over 150 ms in continuous irradiation mode. A slightly but consistently lower aberration yield was observed for the pulsed compared to the continuous mode of proton irradiation. This difference was not statistically significant when each aberration type was analyzed separately (P values between 0.61 and 0.85 in experiment I and P values between 0.32 and 0.64 in experiment II). However, excluding the total aberrations, which were not analyzed as independent radiation-induced effects, the mean ratio of the yields of dicentrics, centric rings and excess acentrics scored together showed (with 95% CI) a significant difference of 0.90 (0.81; 0.98) between the pulsed and the continuous irradiation modes. A similar tendency was also determined for the corresponding RBE values relative to 70 kV X rays. Since the different findings for the comparisons of individual chromosome aberration types and combined comparisons could be explained by different sample sizes with the consequence that the individual comparisons had less statistical power to identify a difference, it can be concluded that 20 MeV protons may be slightly less effective in the pulsed mode.     

基于B超图像评价HIFU治疗剂量对组织损伤程度的影响

基于B超图像分析HIFU治疗中辐照剂量、组织凝固性坏死区域和图像参数之间的关系。通过对高强度聚焦超声辐照新鲜离体组织前后获得的B超图像做数字减影处理,计算图像灰度平均值,同时切片观察并记录生物组织的凝固性坏死区域大小,在此基础上得到大批量数据的统计特性。结果表明：辐照剂量、组织凝固性坏死区域与B超图像灰度平均值在一定范围内成正相关性;当凝固性坏死区域增大到一定程度时,B超图像灰度平均值不再增大,而是呈无规律分布。B超图像灰度可反映组织损伤程度,为实时监控HIFU治疗效果提供依据。     

Determination of the level of internal irradiation of people farming in territories polluted by radionuclides

The derived specific activities of radionuclides in the soil are calculated for different pathways of the internal irradiation at a level of an effective dose of 1 mSv per year. The ratio of the actual specific activity to its derived specific activity gives a value of the contribution to annual effective dose for the considered irradiation pathway. The results of the work make it possible to find the upper estimation of the effective dose by simple measurements of the exposure dose rate in a soil sample of a given geometry and by rate of pulses counting by beta- and alpha-radiometry of thick soil samples.     

An assessment of the radiological impact of the Windscale reactor fire, October 1957

On the 10th and 11 October 1957 a fire in the No 1 Pile at the Windscale establishment in Cumbria led to an uncontrolled release of activity to the atmosphere. The resultant cloud subsequently dispersed and radionuclides could be detected over England, Wales and parts of northern Europe. The extensive environmental measurements which were made during and after the release enabled a fairly accurate estimate to be made of the radiation doses to the most exposed individuals in the local population. Until recently, no estimates of the population dose resulting from the release had been published. This paper describes assessments which have been made by the NRPB of the population or collective dose from the release and of the possible associated health impact. In addition to the fission products that escaped, radionuclides were released from materials undergoing irradiation in the pile at the time of the fire. The assessment has included the results of a review of previously unpublished data which established the quantity of these nuclides released and considers their impact on both individual and population doses. The collective effective dose equivalent commitment from the release is estimated to have been 2.0 x 10(3) man Sv. The route of exposure which contributed the most to the collective dose was the inhalation pathway. Iodine-131 was the most important radionuclide, contributing nearly all of the collective dose to the thyroid and a large part of the collective effective dose. Polonium-210 and caesium-137 also made significant contributions; that from caesium-137 came in the longer term via external irradiation from ground deposits and the ingestion of contaminated foodstuffs. The methodology used in the study has been validated to a certain degree by comparing the predicted levels of individual thyroid activity and those measured directly in the weeks following the accident in London, Leeds and Cumbria.     

Estimates of the efficacy of the local protection of dogs against ionizing radiation

The possibility of prognosis of survival of dogs subjected to acute nonuniform irradiation leading to haemopoietic radiation sickness has been demonstrated. The prognosis is based on the "equal dose" concept that is implemented together with the dose dependence of the bone marrow haemopoiesis activity. The estimates of the consequences of irradiation of dogs, with certain body parts being shielded, have shown a good correlation between the calculation results and the experimental data.     

Differential effects of chronic ingestion of tritiated water on prenatal brain development

Female rats were given tritiated drinking water (3 microCi/ml) from 30 days before mating up to and throughout pregnancy. At this low dose, the course and the outcome of pregnancy were normal. The differences between newborn body and cerebral weights of the treated rats and those of control animals were on the borderline of significance. In contrast, cerebral DNA and cerebral protein were highly significantly lower. In 30-35% of the treated population the DNA and protein values were more than 2 standard deviations (SD) below the mean values for the control population. Thus the number of the progeny of the mothers exposed to tritiated water that were considered to have "outstandingly low" levels of DNA and protein was 14-17 times greater than in the control group. The irradiated population also had 3-5% of severely affected individuals with cerebral DNA and protein values more than 2 SD below the mean of the experimental population. However, even in this irradiated population, a certain number of individuals did not show the effects of radiation as indicated by DNA and protein values that were not lower than the mean values of the control population. These animals may represent those individuals in which normal (control) populations would have cerebral DNA and protein levels well above the average (by 1 to 2 SD), but here, because of prenatal irradiation, were about average. If so, this lack of effect of irradiation cannot be caused by protection against radiation. However, at present, a differential repair mechanism of protection in those animals (or their mothers) that showed little or no effect of irradiation cannot be excluded.     

The radioprotective effect of a hypoxic respiratory mixture (8% O2) for intestinal epithelial stem cells during single and fractionated irradiation of mice]

The method of intestinal "microcolonies" was used to study the radioprotective effect of a gas mixture, containing 8% of O2, on mice subjected to single and fractionated (5 fractions for 30 min) irradiation. The protective effect was indicated by a decreased slope of dose curves of the stem cell injury; the extrapolation number decreased simultaneously. So the values of dose modifying factors (DMF) were higher, when calculated by D0 ratio (where they amounted to 1.76 and 1.39 for single and fractionated exposure respectively), than those determined by equally effective doses (1.19 and 1.26 for single and fractionated effects respectively, which corresponded to LD50/4 when calculated at lg N = 1.9). It is suggested that the radiation response of certain stem cell populations of intestinal epithelium are different: this is attributed to different degrees of hypoxia in cells and to different directions of the hypoxia effects on the injury and the ability of postirradiation repair.     

Post-Chernobyl thyroid cancers in Ukraine. Report 2: risk analysis

On April 26, 1986, the worst nuclear reactor accident to date occurred at the Chornobyl (Chernobyl) power plant in Ukraine. Millions of people in Ukraine, Belarus and Russia were exposed to radioactive nuclides, especially (131)I. Since then, research has been conducted on various subgroups of the exposed population, and it has been demonstrated that the large increase in thyroid cancer is related to the (131)I exposure. However, because of study limitations, quantified risk estimates are limited, and there remains a need for additional information. We conducted an ecological study to investigate the relationship between (131)I thyroid dose and the diagnosis of thyroid cancer in three highly contaminated oblasts in Northern Ukraine. The study population is comprised of 301,907 persons who were between the ages of 1 and 18 at the time of the Chornobyl accident and were living in 1,293 rural settlements in the three study oblasts. Twenty-four percent of the study population had individual thyroid dose estimates and the other 76% had "individualized" estimates of thyroid dose based on direct thyroid measurements taken from a person of the same age and gender living in the same or nearby settlement. Cases include 232 thyroid cancers diagnosed from January 1990 through December 2001, and all were confirmed histologically. Dose-response analyses took into account differences in the rate of ultrasound examinations conducted in the three study oblasts. The estimated excess relative risk per gray was 8.0 (95% CI = 4.6-15) and the excess absolute risk per 10,000 person-year gray was estimated to be 1.5 (95% CI = 1.2-1.9). In broad terms, these estimates are compatible with results of other studies from the contaminated areas, as well as studies of external radiation exposure.     

A comparative analysis of the impact on biota and man in the 30 km zone of the Chernobyl NPP

A methodological approach is described for a comparative assessment of ionizing radiation effects on man and biota, based on the use of indices of radiation impact--ratios of actual exposure doses to environmental objects (including humans) and critical ones. As such doses, standards limiting radiation exposure and doses at which phenotypical effects were absent after the Chernobyl accident were employed, respectively for man and biota. For the test site chosen within the 30 km ChNPP zone (region of the Borshchovka settlement), dose burdens to reference biota species and the population (with and without evacuation) and the corresponding radiation impact indices were calculated. For the long term period after the accident radiation safety standards for man are shown to ensure radiation safety for biota as well. At the same time in the early period after the accident the emergency regulations do not guarantee adequate protection of nature, some species of which can be subject to irradiation more than man, even if countermeasures like evacuation are not applied. A conclusion has been made on the necessity of a more detailed and comprehensive analysis of situations when the anthropocentric principle "if radiation standards protect man then biota are also adequately protected" is violated.     

Radiation injury: some aspects of the oncogenic effects.

The late effects or irradiation stem from cell killing, mutation, and malignant transformation. Cancer is the major somatic late effect of exposure to low dose levels of radiation, and estimates of risk of cancer in man after irradiation are based entirely on human experience. The data for dose-response relationships for the induction of tumors by external irradiation in man have been obtained from a single exposure or a small number of exposures delivered at high dose rates. In contrast, exposure to environmental irradiation is mainly protracted over a long period of time and is delivered at a low dose rate. As yet no allowance has been made for the effect of protraction of the exposure time in estimating the risk of cancer, although an adjustment has been made in the case of estimates of genetic risk. Incidence of tumors has been the only parameter used for risk estimates, but latent period and degree of malignancy, which are probably both dose and dose-rate dependent, influence the nature of the risk from radiation. As the knowledge about the effects of low-level radiation has been accumulated and assimilated over the last 70 years, so has the concern for reasonable standards of safety. There are still problems in the estimation of radiation risks, but at least many of the relevant questions can now be framed. The problems of estimating risks for chemical carcinogens are clearly greater, but the experience gained from radiation studies should help in the design of the necessary experiments.     

The antiradiation properties of the ecdysteroid-containing compounds

The antiradiation properties of the ecdysteroid-containing preparations ("serpisten" and inokosterone) are studied under their application before or after the 22.6 cGy chronic low intensity gamma-irradiation of mice. It is shown that the antiradiation of these compounds depend on the dose of preparations and time of the application before or after irradiation of mice. "Serpisten" prevented the decrease of the growth of the body mass of irradiated mice. The normalization of the phospholipid composition of the mice liver and blood erythrocytes for the most investigated parameters revealed under the application of this compound at the dose of 50 mg/kg after the irradiation of animals. The capacity of "serpisten" to decompose of peroxides is shown in vitro. Inokosterone had the certain anabolic properties, caused the normalization of the total peroxidase activity of blood and intensity of the lipid peroxidation (LPO) in brain and in liver, and also the repair of the interrelation between the LPO intensity and catalase activity in the irradiated mice liver. The obtained results allow to conclude that the antiradiation properties of the ecdysteroid-containing preparations under the chronic low intensity irradiation of animals at the low dose due to their capacity to depend on the LPO regulatory system parameters.     

Current problems of estimation of genetic risk of human exposure to radiation

The methodology of assessing the genetic risk of radiation exposure is based on the concept of "hitting the target" in development of which N.V. Timofeeff-Ressovsky has played and important role. To predict genetic risk posed by irradiation, the UN Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) has worked out direct and indirect methods of assessment, extrapolational, integral and populational criteria of risk analysis that together permit calculating the risk from human exposure on the basis of data obtained for mice. Laboratory mice are the main objects in studying radiation mutagenesis due to the fact that the data on the frequency of radiation-induced human mutations are rather scarce. The method of doubling dose based on the determination of a dose doubling the level of natural mutational process in humans is the main one used to predict the genetic risk. The evolution of views about the genetics risk of human exposure to radiation for last 40 years is considered. Till 1972 the main model for assessing the genetic risk was the "human/mouse" model (the use of data on the spontaneous human variability and data on the frequency of induced mutations in mice). In the period form 1972 till 1994 the "mouse/mouse" model was intensively elaborated in many laboratories. This model was also used in this period by UNSCEAR experts to analyze the genetic risk from human irradiation. Recent achievements associated with the study of the molecular nature of many hereditary human diseases as well as the criticism of number fundamental principles of the "mouse/mouse" model for estimating the genetic risk on a new basis. The estimates of risk for the different classes of genetic diseases have been obtained using the doubling-dose method. The estimate of doubling dose used in the calculations is 1 Gy for low dose/chronic low-LET radiation conditions.     

Effects of chronic irradiation of Scots pine (Pinus sylvestris L.) in Chernobyl exclusion zone

The quantitative "dose rate-effect" dependences are presented for the cytogenetic damages in the seedlings and apical meristem of Scots pine growing in the Chernobyl zone. The specific patterns of dynamics of formation of the morphological effects in the studied species are considered for the conditions of the internal and external chronic irradiation. The correlation dependencies are established for the irradiation effects appearing at the morphological and cell level. The assumption concerning the mechanism of the morphological changes formation is done.     

The disruption of aquaporin function in cell membranes as a cause of changes in germinability of pea seeds after exposure to low doses of gamma-radiation

Pea seeds (Pisum sativum L.) from the seed lot with 80% germinability were separated in fractions according to room temperature phosphorescence: strong seeds were assigned to fraction I, and weak seeds formed to fraction II. During imbibition, the seeds of fraction II exhibited twofold higher rates of water uptake and experienced hypoxia. Some of these seeds suffocated from hypoxia, and other seeds produced seedlings with morphological defects (such seeds were considered incapable of germination). One week after irradiation with the dose of 3 Gy, germination percentage decreased to 45%, which was caused by the increase of number of weak seeds. The germinability of seeds subjected to gamma-irradiation at doses of 7 and 10 Gy was similar to that of control seeds. In these sub-lots, there appeared so-called "improved" seeds, which were similar to non-irradiated seeds in terms of phosphorescence level, the rate of water uptake and germination percentage. It was shown with the use of PCMB that the difference in the rates of water uptake by seeds of fraction I and II depended on the permeability of cell membranes. The permeability was determined by the state of aquaporins ("open"-"closed"). The experiments with phosphatase inhibitor (NaF) shown that in seeds irradiated with dose of 3 Gy (fraction II), the mechanism of aquaporins closing was broken (phosphatase was inactivated). In "improved" seeds (after irradiation with dose of 10 Gy), aquaporins were closed irreversibly in air-dry state, when aquaporin dephosphorylation was unlikely. It was concluded that the abnormal increase (following the initially decrease) in germination of pea seeds after irradiation can be explained without invoking the hypothesis on hyper function of reparatory mechanism of at low doses of irradiation.     

The "shielding" effect of the guide wire during coronary brachytherapy with P-32 source

Intracoronary beta irradiation (use of beta radiation for intracoronary irradiation) is an effective method in reducing neointimal proliferation after successful angioplasty and stent implantation. However, long-term results may be influenced by absolute dose and by the homogeneity in dose distribution. In our study, we investigated dose perturbation due to the presence of a conventional guide wire during irradiation. The Galileo III centering catheter and P-32 beta source were used. The 55 MD GAF Chromic foil was positioned within a phantom made of PMMA. The dose distribution at cylindrical surfaces has been assessed using GAF Chromic dosimetric foil MD55 (Nuclear Associates, USA). Our study demonstrated the significant dose reduction of 46% in the most "shaded" area. The dose reduction to 80% or less occupy the 60 degrees sector. This phenomenon can cause progression of late restenosis. In conclusion, the results suggest that technical improvements in centering catheter construction should be made to eliminate the "shielding" effect of the guide wire.     

Radiation protection of the environment: anthropocentric and eco-centric principles

The second half of the XX century was dominated in the field of radiation protection of the environment by the anthropocentric concept stated by the International Commission on Radiological Protection (ICRP). According to this concept "if man is adequately protected by radiological standards then biota are also adequately protected". At the end of the XX--beginning of the XXI centuries in the area of area of radiation protection of nature an ecocentric strategy is beginning to develop where emphasis has swung to the protection of biota in their environment. Inadequacy of ICRP's anthroposentric concept is reported. Issues are discussed such as ecological dosimetry, nonequidosal irradiation of man and biota, criteria for estimating radiation induced changes in biota and man, as well as the need to harmonize permissible exposure doses to man and biota. An urgent need is stressed to develop a single (synthetic) concept of radiation protection which simultaneously ensures protection of human health and biota well-being in their environment. This concept is to be based on the recognition of the integrity of socio-natural ecosystems where man and biota are considered as a unity.     

In vivo effects of γ-irradiation on the functional architecture of the lampbrush chromosomes in Pleurodeles (Amphibia,Urodela)

In vivo irradiation of ovaries of Pleurodeles poireti by -rays leads to structural rearrangement of lampbrush chromosomes in late vitellogenic oocytes (stages V and VI). The loops collapse into the chromomeres and the axes condense. Doses between 200 and 2,000 rads have been tested. We observed that such changes were dependent on the irradiation dose though the chronological order of the events was irrespective of the dose. The maximum effect was attained about 10 h after irradiation. The alterations are totally reversible. Over a period of 3 days, chromosomes gradually relax, regenerate loops and recover their normal appearance. In mid vitellogenic oocytes (stages III and IV) lampbrush chromosomes do not undergo radiation induced alterations. It seems that only full-grown oocytes are competent to respond to the ionizing-flow.