Inhibition of gastric secretion in guinea pig by relatively low dose ionizing radiation

We evaluated the effect of a single dose of ionizing radiation on gastric secretion in awake guinea pigs equipped with a permanent gastric cannula. Changes in gastric secretion were measured using a dye dilution technique. Infusion of histamine increased acid and fluid output and there was a positive correlation (r = 0.93) between the two. Total body irradiation with 400 cGy, like cimetidine, suppressed acid and fluid secretion under basal conditions and during histamine stimulation by 50-90%. Recovery from the radiation damage was only partial after one week. Irradiation inhibited the rise in gastric juice volume during histamine stimulation and also reduced the normal gain in body weight of the guinea pig. These results demonstrate that ionizing radiations have an immediate and long lasting effects on the gastric mucosal function of the guinea pig.     

Metabolomic response of human skin tissue to low dose ionizing radiation

Understanding how human organs respond to ionizing radiation (IR) at a systems biology level and identifying biomarkers for IR exposure at low doses can help provide a scientific basis for establishing radiation protection standards. Little is known regarding the physiological responses to low dose IR at the metabolite level, which represents the end-point of biochemical processes inside cells. Using a full thickness human skin tissue model and GC-MS-based metabolomic analysis, we examined the metabolic perturbations at three time points (3, 24 and 48 h) after exposure to 3, 10 and 200 cGy of X-rays. PLS-DA score plots revealed dose- and time-dependent clustering between sham and irradiated groups. Importantly, delayed metabolic responses were observed at low dose IR. When compared with the high dose at 200 cGy, a comparable number of significantly changed metabolites were detected 48 h after exposure to low doses (3 and 10 cGy) of irradiation. Biochemical pathway analysis showed perturbations to DNA/RNA damage and repair, lipid and energy metabolisms, even at low doses of IR.     

Modeling radioprotective mechanisms in the dose effect relation at low doses and low dose rates of ionizing radiation

A new model (Random Coincidence Model--Radiation Adapted (RCM-RA)) is proposed which explains a possible pseudo threshold for stochastic radiation effects. It describes the formation of cancer in the case of multistep fixation of lesions in the critical regions of tumor associated genes such as proto-oncogenes or tumor-suppressor genes. The RCM-RA contains two different possibilities of DNA damage to complementary nucleotides. The damage may be caused either by radiation or by natural processes such as cellular radicals or thermal damage or by chemical cytotoxins. The model is based on the premise that radiation initially is bionegative, damaging organisms at their different levels of organization. The radiation, however, also induces various cellular radioprotective mechanisms which decrease the damage by natural processes. Considering both effects together, the theory explains apparent thresholds in the dose-response relation for radiation carcinogenesis without contradiction to the classical assumption that radiation is predominantly bionegative at doses typically found in occupational exposures.     

Bone marrow hemopoiesis at emotional stress reactions of various intensity upon a background of exposure to low dose ionizing radiation

Rats preliminary exposed to 0.9 Gy of ionizing radiation showed disturbances in the development of adaptive reactions of blood system to emotional stress, compensatory capacity of the blood system being decreased. A degree of the disturbances directly depended on the duration and intensity of the emotional stress: at the prolonged intensive emotional stress a sharp decrease in the adaptive and compensatory capacity of blood system was found; at short intensive or moderate stress the changes in the adaptive and compensatory capacity of hemopoiesis were less pronounced. A combined action of low-dose ionizing radiation and short weak emotional stress did non affect the adaptive and compensatory capacity of hemopoietic system.     

Mediator function of molecular factors--lipoxygenase enzyme systems during exposure to ionizing radiation

This paper, which is a review of the national literature on the mediatory function of lipoxygenase systems affected by ionizing radiation, reports data on the functional role of lipoxygenases, their regulator--mediate contribution to radiation response of plants and animals. The latest data are submitted concerning the biological regulatory systems, eicosanoids--leukotrienes, formed under the effect of lipoxygenases which catalyse oxidation of polyunsaturated arachidonic acid (20:4). The structure and function of leukotrienes are described for these are necessary in studying the biochemical functions of lipoxygenases after ionizing irradiation. Emphasis is made on biologically active leukotrienes which take part in biological processes involved in inflammatory and hypersensitive reactions under the effect of radiation. Possible involvement of the lipoxygenase systems in metabolism regulation, its resistance and activation in a living body during development of radiopathological processes are discussed. The modelling concepts are considered for perspective radiation research aimed at biotechnological utilisation of lipoxygenases. Some regularities of mediatory function of lipoxygenase systems have been found. An assumption has been made that lipoxygenases and leukotrienes play an important role in the life of irradiated cells and tissues.     

Epigenetic cell reactions induced by ionizing radiation

The importance of radiation modification of epigenetic activity in the general mechanism of radiobiological reactions is proved. The inheritable epigenetic changes induced by irradiation are one of the basic reasons of formation of the remote radiation pathology. It is noted that epigenetic inheritable changes of cells have the determined character distinguishing them from mutation changes, being individual and not directed. It is underlined the ability of ionizing radiation to modify a level of spontaneous genetic instability inherited in a number of cell generations on the epigenetic mechanism.     

Wound trauma alters ionizing radiation dose assessment

ABSTRACT: BACKGROUND: Wounding following whole-body gamma-irradiation (radiation combined injury, RCI) increases mortality. Wounding-induced increases in radiation mortality are triggered by sustained activation of inducible nitric oxide synthase pathways, persistent alteration of cytokine homeostasis, and increased susceptibility to bacterial infection. Among these factors, cytokines along with other biomarkers have been adopted for biodosimetric evaluation and assessment of radiation dose and injury. Therefore, wounding could complicate biodosimetric assessments. RESULTS: In this report, such confounding effects were addressed. Mice were given 60Co gamma-photon radiation followed by skin wounding. Wound trauma exacerbated radiation-induced mortality, body-weight loss, and wound healing. Analyses of DNA damage in bone-marrow cells and peripheral blood mononuclear cells (PBMCs), changes in hematology and cytokine profiles, and fundamental clinical signs were evaluated. Early biomarkers (1 d after RCI) vs. irradiation alone included significant decreases in survivin expression in bone marrow cells, enhanced increases in gamma-H2AX formation in Lin+ bone marrow cells, enhanced increases in IL-1beta, IL-6, IL-8, and G-CSF concentrations in blood, and concomitant decreases in gamma-H2AX formation in PBMCs and decreases in numbers of splenocytes, lymphocytes, and neutrophils. Intermediate biomarkers (7 - 10 d after RCI) included continuously decreased gamma-H2AX formation in PBMC and enhanced increases in IL-1beta, IL-6, IL-8, and G-CSF concentrations in blood. The clinical signs evaluated after RCI were increased water consumption, decreased body weight, and decreased wound healing rate and survival rate. Late clinical signs (30 d after RCI) included poor survival and wound healing. CONCLUSION: Results suggest that confounding factors such as wounding alters ionizing radiation dose assessment and agents inhibiting these responses may prove therapeutic for radiation combined injury and reduce related mortality.     

Effect of ionizing radiation with low dose rate on glyco- and mucoprotein metabolism in dogs

In experiments on dogs exposed to radiation doses of 2.45--7.35 Gy during 2 to 6 years, it was demonstrated that oxidation of glyco- and mucoproteins in lungs, skin, cartilaginous tissue and elastic ligament was impaired. It is suggested that the compensatory processes come into play in the lungs and skin.     

Transposition of chromosome loci in bystander cells upon exposure to an adaptive dose of ionizing radiation

During the process of the realization of the bystander effect the trans of the Signal from irradiated cells to the intact cell (bystander cells) happens. So both type of cells (irradiated and intact cells) have the same damages and reactions. There are new data about bystander effect as the transduction mechanism of the adaptive response and we have investigated this phenomenon. There are an incubation of the intact (bystander cells) and the exposed (X-radiation of 10 cGy) human lymphocytes and we analyze the location of the centromeric loci of the first chromosome. We observed hat for the first time that after X-ray exposition of the adaptive doses the transposition of the chromosome loci from the peripheral to the central parts of the nucleus in intact (bystander cell) G0-lymphocytes which were incubated in the growth environment cells with irradiated cells removal. We support that the starting states of the adaptive response is the loci extrication of the matrix, the transposition and the approach homologous chromosomes. This process is necessary for the DNA double strand breaks reparation (in the case of injured dose X-radiation) with the participation of the homologous recombination.     

Rapid dicentric assay of human blood lymphocytes after exposure to low doses of ionizing radiation

The probability of losses of different chromosome aberrations during the dicentric chromosome assay of metaphase cells with incomplete sets of chromosome centromeres was estimated using a mathematical model for low doses of ionizing radiation. A dicentric assay of human blood lymphocytes without determination of the total amount of chromosome centromeres in cells without chromosome aberrations (rapid dicentric assay) has been proposed. The rapid dicentric analysis allows to register chromosome aberrations in full compliance with the conventional classification. The experimental data have shown no statistically significant difference between the frequencies of dicentric chromosomes detected by rapid and classical dicentric chromosome assays of human lymphocytes exposed to 0.5 Gy of 60Co gamma-rays. The rate of the rapid dicentric assay was almost twice as high as that of the classical dicentric assay.     

Inhibition of mammalian cell DNA synthesis by ionizing radiation

A semi-log plot of the inhibitory effect of ionizing radiation on the rate of DNA synthesis in normal mammalian cells yields a two-component curve. The steep component, at low doses, has a D0 of about 5 Gy and is the result of blocks to initiation of DNA replicons. The shallow component, at high doses, has a D0 of greater than or equal to 100 Gy and is the result of blocks to DNA chain elongation. The target size for the inhibition of DNA replicon initiation is about 1000 kb, and the target size for inhibition of DNA chain elongation is about 50 kb. There is evidence that the target for both components is DNA alone. Therefore, the target size for inhibition of DNA chain elongation is consistent with the idea that an effective radiation-induced lesion in front of the DNA growing point somehow blocks its advance. The target size for inhibition of DNA replicon initiation is so large that it must include many replicons, which is consistent with the concept that a single lesion anywhere within a large group (cluster) of replicons is sufficient to block the initiation of replication of all replicons within that cluster. Studies with radiosensitive human cell mutants suggest that there is an intermediary factor whose normal function is necessary for radiation-induced lesions to cause the inhibition of replicon initiation in clusters and to block chain elongation; this factor is not related to poly(ADP-ribose) synthesis. Studies with radiosensitive Chinese hamster cell mutants suggest that double-strand breaks and their repair are important in regulating the duration of radiation-induced inhibition of replicon initiation but have little to do with effects on chain elongation. There is no simple correlation between inhibition of DNA synthesis and cell killing by ionizing radiation.     

Estimating the lowest detectable dose of ionizing radiation by FISH whole-chromosome painting

Chromosome translocations are the hallmark of exposure to ionizing radiation, but they also occur spontaneously, and their frequencies increase dramatically with age. This complicates dosimetry unless a pre-exposure sample is available for each putatively exposed individual. Here we use published values for translocations in unexposed subjects from a wide range of ages, together with data from an in vitro (137)Cs dose-response curve, to estimate the minimum dose of whole-body radiation that is detectable by translocation analyses in individuals of a given age. For subjects aged 20 to 69 years, we show that the minimum detectable acute dose increases linearly with age at a rate of 0.179, 0.218 and 0.256 cGy per year for significance levels of P = 0.05, P = 0.01 and P = 0.001, respectively. For chronic exposures, the corresponding minimum detectable doses are 1.591, 2.270 and 3.055 cGy per year. For newborns, the 95th and 99th percentiles of translocation frequencies are 0.20 and 0.31 per 100 cell equivalents, respectively, indicating that values greater than these are consistent with exposures at P = 0.05 and P = 0.01, respectively. These results improve our understanding of the requirements and limitations for performing biological dosimetry when only the age of the exposed individual is known.     

The effects of low doses of low-intensity ionizing radiation on DNA structure and function

Chronic effects of low doses of low-intensity ionizing radiation (IR) on biological objects have gained great social significance. This has given a considerable impetus to research into the biological effects and mechanisms of such exposures, both in Russia and abroad. In this paper, an overview of the physicochemical and molecular basis of IR influence at low doses is provided. Means of cell protection from radiation damage are studied and an analysis of the typical features and differences in the radiation effects at low and high doses is carried out. We considered DNA radiation damage, both in cell cultures and in vivo, as well as the processes and results of their repair. Particular attention is paid to changes in the basic paradigms of biological radiation effects at low doses.     

Tissue reactions under chronic exposure to ionizing radiation

Reviewed are radiobiological data on the emergence of tissue reactions that may determine the course and outcome of human chronic irradiation. The main mechanisms of the reaction of hemopoietic, immune, reproductive, endocrine, respiratory systems and skin to long-term and fractionated exposure to ionizing radiation are considered. The problem of developing a new approach to threshold dose estimation for chronic exposure effects is discussed.     

Effect of low dose rate radiation on cell growth kinetics.

Experimental determinations were made of cell number as a function of time for two strains of L5178Y mammalian cells maintained continuously in various environments of radiation. One strain possessed a shoulder in its dose response curve whereas the other did not. Neither strain showed any significant difference in growth rate for interdivision doses on the order of the median lethal dose or less delivered continuously at a low dose rate or pulsed every 4 h at a high instantaneous dose rate. It was also shown that large numbers of dead cells have little effect on growth rate and that these dead cells last as discrete entities for many days. A simple theory of growth rate in the presence of radiation is presented, and the agreement with the observations implies that there is no effect of any sublethal low dose rate radiation received in one generation on the growth rate or radiation sensitivity of the succeeding generation. Further analysis of the data also showed that for the no-shoulder cells at 37 degrees C, tritiated water had a relative biological effect close to unity for cell sterilization.     

Immunocorrective action of tuftsin during exposure to ionizing radiation

The effect of the tetrapeptide tuftcin (Thr-Lys-Pro-Arg) on the humoral immune response in CBA mice exposed to sublethal irradiation in a dose of 450 sGy was studied. The drug was injected intraperitoneally for 5 days before (series I) or after (series II) radiation exposure. It has been shown that taftcin has no protective action but decreases considerably the immune response lowering due to radiation.     

Toxicity and mutagenicity of low dose rates of ionizing radiation from tritiated water in human lymphoblastoid cells

In order to study the toxic and mutagenic effects of low-dose-rate exposure to ionizing radiation, human lymphoblast cells were grown continuously in tritiated water (3H2O) for up to 8 days. Dose rates ranged from 0.0054 to 0.064 rad/min. Mutation to trifluorothymidine resistance (TK locus) and 6-thioguanine resistance (HGPRT locus) was measured; comparable results were observed at both loci. The mutant fraction as a function of total absorbed dose was independent of dose rate over the range studied. At the lower doses, the dose-response curve was linear, with no indication of a threshold. Overall, it appeared to be slightly biphasic with a diminished slope at higher total doses. These data are discussed in relation to earlier studies utilizing high-dose-rate X-irradiation and incorporated [3H]TdR; 3H2O and [3H]TdR were more mutagenic per rad than X-rays, but 3H2O was less cytotoxic than either X-rays or [3H]TdR.