Effect of Ionizing Radiation on Immunity

Ionizing radiation has a deleterious effect on the immunity mechanism, particularly when large but sublethal doses are applied over a short period of time. The hematopoietic system is extremely sensitive, and a fall in the lymphocytes is one of the most characteristic manifestations. The normal balance of the microflora of the intestinal and respiratory tracts is disturbed, which results in a bacteremia and may lead to death of the host. Active immunity is seriously interfered with if the irradiation occurs shortly before the injection of an antigen. There is also reduced resistance to pathogenic micro-organisms, which may lead to fatal infections. Prolonged irradiation at low levels does not seem to affect immunity adversely. Active immunization should be carried out well in advance of exposure to radiation, and supportive treatment commenced immediately after exposure to large doses.     

Exposure to low dose of gamma radiation enhances the excision repair in Saccharomyces cerevisiae

The effect of low doses of ionizing and nonionizing radiation on the radiation response of yeast Saccharomyces cerevisiae toward ionizing and nonionizing radiation was studied. The wild-type strain D273-10B on exposure to 54 Gy gamma radiation (resulting in about 10% cell killing) showed enhanced resistance to subsequent exposure to UV radiation. This induced UV resistance increased with the incubation time between the initial gamma radiation stress and the UV irradiation. Exposure to low doses of UV light on the other hand showed no change in gamma or UV radiation response of this strain. The strains carrying a mutation at rad52 behaved in a way similar to the wild type, but with slightly reduced induced response. In contrast to this, the rad3 mutants, defective in excision repair, showed no induced UV resistance. Removal of UV-induced pyrimidine dimers in wild-type yeast DNA after UV irradiation was examined by analyzing the sites recognized by UV endonuclease from Micrococcus luteus. The samples that were exposed to low doses of gamma radiation before UV irradiation were able to repair the pyrimidine dimers more efficiently than the samples in which low gamma irradiation was omitted. The nature of enhanced repair was studied by scoring the frequency of induced gene conversion and reverse mutation at trp and ilv loci respectively in strain D7, which showed similar enhanced UV resistance induced by low-dose gamma irradiation. The induced repair was found to be essentially error-free. These results suggest that irradiation of strain D273-10B with low doses of gamma radiation enhances its capability for excision repair of UV-induced pyrimidine dimers.     

Quantitative relationships of the harmful effect of ionizing radiation on natural resistance of the organism to various infectious agents. Review of literature.

On the basis of an analysis of data from the literature and our own experimental results, the conclusion can be drawn that there is inverse linear dependence between the dose of irradiation and natural resistance of the organism to infection with various infectious agents. With increasing doses of irradiation, the irradiated organism is exposed to greatest risk from the part of the agents of intestinal infections and representatives of normal microflora. These are followed by agents of various diseases of microbial nature. The least decrease can be observed in resistance to viruses.     

Cytogenetic effects of UV laser radiation with wavelengths of 248, 223 and 193 nm on mammalian cells

Ten hours after irradiation of mouse cornea with doses of 0.09 to 1.5 J/cm2 the incidence of cells with chromosome aberrations increased linearly with dose and amounted to 11.7% at 248 nm, 5.5% at 223 nm and 2.6% at 193 nm per 1 J/cm2. No induced chromosome aberrations occurred 72 hr following irradiation. Within the dose range from 3.0 to 18 J/cm2 the cytogenetic effect of radiation was less manifest than that with the doses mentioned above, the frequency of chromosome aberrations being independent of either wave length or radiation dose and amounted to 2.5 to 3.0%.     

Effect of the spaceflight radiation factor on the growth of Brassica pekinensis and micromycetes Fusarium oxysporum

The effects of chronic exposure in the combination of low-dose gamma- and neutron radiation on growth of Brassica pekinensis (lour) Rupr, var. Khibinskaya, and micromycetes of Fusarium oxysporum, a representative of soil microflora were stadied. Seeds, water and vegetating plants raised from previously irradiated seeds were subjected to radiation exposure. The gamma-neutron dose rate was -0.013 sGy/d and the neutron flux was -20 n/cm2 d. Growth of Brassica pekinensis and of Fusarium oxysporum on the background of weak chronic ionizing irradiation by radioactive nuclides was noticeably changed when compared with the growth in the normal radiation environment. The radiosensitivity of Fusarium oxysporum isolated from the artificial soil following 60-d exposure was far higher than the radioactivity of the culture isolated from non-irradiated soil. Fusarium oxysporum isolated from the irradiated soil failed to form spores normally even when cultivated in a non-irradiated nutrient substrate without further exposure. These peculiarities persisted at least for four months. 15-mo gamma- and neutron exposure of Brassica pekinensis seeds held in storage for 5 years retained their original germinating capacity, whereas the non-irradiated seeds suffered deprivation of this quality. It was noticed that the Brassica pekinensis reaction on chronic exposure of low doses was markedly dependent on the growth conditions non-related directly with the radiation background.     

Action of x-ray irradiation on the nuclear envelope of rat liver cells]

X-irradiation of isolated nuclear envelopes (NE) has revealed their high radiosensitivity, while irradiation of isolated intact nuclei in vitro, in the doses up to 5000 r 18--20 hours after partial hepatectomy, produced no morphological changes in NE. The damaging effect of irradiation on both nuclei and mitochondria (Mt) was revealed only with a decrease in cytochrome-c-oxidase (CO) activity in parallel with an increase in the radiation dose. One hour after the whole body irradiation of rats in the beginning of S-period, the damaging effect was recorded in both NE and Mt at the doses of 50 and 150 t, and was enhanced with the increase of irradiation dose. Morphological changes were observed mostly in the outer nuclear membrane, which lost its distinct outline and disappeared from some nuclear regions. Lethal radiation doses produced a decrease in the number of pore complexes (PC) with their evident segregation from the membranes. After irradiation in a dose of 1200 r, only the residue or "ghosts" of the PCs remained. After irradiation in doses up to 400 r, the CO-activity recovered during the first hour in Mt and during first two hours in the nuclei.     

Effect of preliminary chronic irradiation and alpha-tocopherol on the frequency of chromosome aberrations in mouse bone marrow cells, induced by exposure to acute gamma-irradiation

The incidence of chromosome aberrations in bone marrow cells of femur did not exceed the spontaneous one in CBA mice exposed, during 70 days, to gamma-radiation at dose--rates of 33.7-35.8 nA/kg and cumulative dose of 2.75 Gy. A single acute exposure of intact animals to a dose of 2.98 Gy increased significantly the mutation level. Preirradiation with small doses increased the resistance of hereditary structures to sublethal radiation doses. Exogenous alpha-tocopherol (0.06 mg/20 g mass) protected the genetic apparatus of cells from total-body irradiation and was an additional factor decreasing the mutation level after acute exposure of mice at the background of long-term irradiation with small doses.     

The enhanced radioresistance (adaptive response) in vivo of splenic colony-forming units (CFU-S) following the exposure of mice to 60Co gamma rays at low doses]

An increase of resistance to radiation damage of human lymphocytes previously exposed to low doses of ionizing radiation from incorporated tritiated thymidine was observed by G. Olivieri et al. in 1984. The phenomenon was named adaptive response and its occurrence was reported by others for many animal and plant cells. In this research we studied the adaptive response of spleen colony formation at different time after previous irradiation of mice with low doses of 60Co gamma rays. Our results suggest that the pretreatments protect spleen colony-formatting units (CFU-S) from the second damaging radiation dose of 1.5 Gy during long time (as many as one month).     

The anti-infective action of immunoglobulins administered at delayed times after irradiation

In experiments with CBA and CBA X C57Bl(F-1) mice it was shown that the radio-protective efficacy and the anti-infectious influence of homo- and heterologous immunoglobulin (IG) applied one, two and three times in the period from 4h to 9 days following irradiation with doses of LD80-95/30. This was displayed by the increased survival rate and normalization of intestinal microflora in treated animals in comparison with untreated ones. Heterologous IG administered at varying times (5 to 20 days) after irradiation with the dose of 4.8 Gy increased the resistance of treated mice to infection with living E. coli culture.     

A re-examination of the effects of ionizing radiation on lifespan and transformation of human diploid fibroblasts.

Human diploid fibroblasts, strain MRC-5, were sequentially irradiated with 60Co gamma rays at intervals during their in vitro lifespan. The results indicate that 3 or 6 doses of 1 Gy can increase lifespan, and the same was true for cells treated with 3 doses of 3 Gy. Higher doses (5 x 3 Gy) did reduce growth potential, suggesting either that mid-late passage cells become more sensitive to radiation, or that doses beyond a given threshold reduce population lifespan by multiple cellular hits. The life extension induced by gamma rays might be due to an induced hypermethylation of DNA. Alternatively, oxygen radicals produced by irradiation might trigger an adaptive stress response which would remove damaged macromolecules and thereby increase the cells' growth potential. Whichever explanation is correct, the results show that the human fibroblast system is not appropriate for the study of the well known effect of ionizing radiation in shortening the lifespan of experimental animals. Contrary to earlier published results, populations of cells treated with cumulative doses of 15 Gy or 18 Gy and held for nearly 3 months after they had reached senescence (Phase III), produced no foci of transformed cells.     

Late effects of abdominal radiation on intestinal uptake of nutrients

The late effects of variable doses of abdominal irradiation on in vitro jejunal uptake were examined. The uptake of glucose, galactose, cholic acid, medium-chain length fatty acids, and decanol was studied 6 and 33 weeks following 300, 600, or 900 cGy abdominal irradiation. The intestinal morphological characteristics were similar 6 and 33 weeks after radiation. The uptake of cholic acid was unaffected by abdominal irradiation, but for glucose, galactose, and four fatty acids the direction and magnitude of the changes in uptake were influenced by the dose of irradiation and by the interval following exposure. The greater uptake of decanol at 6 weeks but lower uptake of decanol at 33 weeks reflected changes in the resistance of the intestinal unstirred water layer. These absorption changes suggest that the intestine may not be capable of correcting the transport abnormalities arising from sublethal doses of abdominal irradiation.     

Radiation factors and their influence on induction of oxygen resistance

Shortly after gamma irradiation, flour beetles exhibited a decline in resistance to oxygen toxicity. Then, about 2 weeks after irradiation, the 50% lethal dose (LD50) exposure time in pure oxygen was much greater than that of nonirradiated beetles, and this enhanced resistance persisted for about 6 months. The magnitude of the enhancement was a function of dose, decreased with increasing age at irradiation, and was modified by radiation factors. Both dose protraction and dose fractionation reduced the development of oxygen resistance to approximately the same degree that it reduced acute radiation lethality. This suggests that both the initial sensitization and the later enhancement of resistance are correlated with the residual biological damage rather than with the physical dose or initial damage.     

Some radiobiological effects in higher plants growing on the territory of the East Ural Radioactive Trace

The spontaneous level of cytogenetic damage in three plant species (Achyrophorus maculatus (Scop.) L.; Plantago lanceolata L.; and Plantago media L.) growing on the territory of the East Ural Radioactive Trace is studied. The radiation resistance of plants from radioactive and control nonpolluted sites is determined. The effects of additional fractionated irradiation at different doses and the role of antioxidant systems in the formation of the radioprotector effect are examined. It is shown that the level of the mutation process in the plant population growing at the radiation polluted sites is increased compared to the control populations from nonpolluted territories. Additional acute γ irradiation of seeds collected from polluted and nonpolluted territories demonstrates improved radiation resistance of the plants from the polluted territory. In the control population of A. maculatus in the versions with a one-hour interval between fractions, the radiation effect follows the additivity principle; at the same time, at a one-day interval between fractions, a highly significant radioprotective effect is manifested clearly in the experimental population. For higher plants, the enhanced effectiveness of the functioning of the antioxidant systems in plants growing on territories contaminated with radiation is shown for the first time. Thus, the radioprotector mechanisms of low-dose chronic and preliminary irradiation are similar and one of these mechanisms is activation of the antioxidant systems in plants growing under conditions of chronic low-intensity irradiation for long periods of time.     

Effects of prolonged low-intensity irradiation on organ weight of the male rat reproductive system

The effects of prolonged irradiation at accumulated doses from 0.5 to 6.0 Gy (dose rate 3.03 cGy/day) on reproductive organs' weight (testes, epididymises, seminal vesicles, prostate) of male rats starting from the early ontogenetic period were studied. On the first day after the irradiation with 1.0 Gy dose a significant loss of the weight in testes and epididymises was revealed. This leaded to the marked atrophy of the organs with the increase of the radiation dose. Long-term restoration of the weight of testes and epididimyses was registered. It was not completed during three months after radiation exposure at 2.0 Gy and higher doses for epididimyses and 4.0-6.0 Gy for testes. The respective changes in the seminal vesicles and prostate weight were less pronounced and had more complicated character. However in the distant period (30-90 days of postreatment) after exposure to 2.0 Gy these parameters were noticeably decreased.     

Inactivation of Escherichia coli O157:H7 in Apple Juice by Irradiation

Three strains (932, Ent-C9490, and SEA13B88) of Escherichia coli O157:H7 were used to determine the effectiveness of low-dose gamma irradiation for eliminating E. coli O157:H7 from apple juice or cider and to characterize the effect of inducing pH-dependent, stationary-phase acid resistance on radiation resistance. The strains were grown in tryptic soy broth with or without 1% dextrose for 18 h to produce cells that were or were not induced to pH-dependent stationary-phase acid resistance. The bacteria were then transferred to clarified apple juice and irradiated at 2°C with a cesium-137 irradiator. Non-acid-adapted cells had radiation D values (radiation doses needed to decrease a microbial population by 90%) ranging from 0.12 to 0.21 kGy. D values increased to 0.22 to 0.31 kGy for acid-adapted cells. When acid-adapted SEA13B88 cells were tested in five apple juice brands having different levels of suspended solids (absorbances ranging from 0.04 to 2.01 at 550 nm), radiation resistance increased with increasing levels of suspended solids, with D values ranging from 0.26 to 0.35 kGy. Based on these results, a dose of 1.8 kGy should be sufficient to achieve the 5D inactivation of E. coli recommended by the National Advisory Committee for Microbiological Criteria for Foods.     

Late functional and biochemical changes in mouse lung after irradiation: differential effects of WR-2721

The radioprotective effect of WR-2721 on late damage after whole thorax irradiation has been studied after split doses of radiation using the standard death and breathing rate assays at monthly intervals between 3 and 15 months after irradiation, as well as two biochemical measurements of injury at 15 months, hydroxyproline (HP), an indicator of tissue fibrosis, and DNA content, an indicator of tissue cellularity. A comparison of HP/lung and breaths per minute (BPM) in each dose group in the WR-2721 and non-WR-2721-treated mice 15 months after irradiation showed that the relationship between these two assays of late lung injury was not the same. There were large dose-related increases in breathing rate corresponding to relatively small changes in HP in the lungs of mice given radiation alone. In contrast, the mice given WR-2721 before irradiation showed large dose-related increases in HP/lung, but BPM remained relatively constant independent of dose. These data suggest then that changes in breathing rate and deaths later than 9 months after whole lung irradiation may not be due to collagen accumulation in the lung. WR-2721 did protect better against late lung functional changes (protection factors (PF) = 1.6) and late deaths (PF = 1.51) than against earlier changes in these same assays (PF = 1.4 and 1.28, respectively). Although the earlier-appearing injury after whole thoracic irradiation is most likely related to lung damage with deaths and increases in breathing rate resulting from pneumonitis, the cause of the late-appearing functional injury in the lung after radiation is not clear. Thus protection of late lung damage measured from either lethality or breathing rate is not related to the prevention of lung fibrosis.     

Increased Radiation Resistance of Vegetative Bacillus pumilus

A 4.5-fold increase in vegetative cell radiation resistance of Bacillus pumilus E601, the internationally recognized biological standard for irradiation sterilization, was obtained by the repeated passage of resistant survivors through successive sublethal doses of (60)Co irradiation. This increase in resistance was accompanied by a corresponding increase in spore resistance through the seventh irradiation passage. By the fifteenth passage, the ability for spore formation was lost. Other effects noted by the successive irradiation dosages included loss of motility and pellicle formation, and changes in the Gram reaction, cell morphology, and colonial morphology. Increased resistance was also accompanied by an increased nutritional requirement for specific amino acids. Radiation resistance was not transferred from vegetative cells to spores.     

Repair of ultraviolet light-induced damage in Micrococcus radiophilus, an extremely resistant microorganism.

Repair of ultraviolet radiation damage was examined in an extremely radioresistant organism, Micrococcus radiophilus. Measurement of the number of thymine-containing dimers formed as a function of ultraviolet dose suggests that the ability of this organism to withstand high doses of ultraviolet radiation (20,000 ergs/mm2) is not related to protective screening by pigments. M. radiophilus carries out a rapid excision of thymine dimers at doses of ultraviolet light up to 10,000 ergs/mm2. Synthesis of deoxyribonucleic acid is reduced after irradiation, but after removal of photodamage the rate approaches that in unirradiated cells. A comparison is drawn with Micrococcus luteus and M. radiodurans. We conclude that the extremely high resistance to ultraviolet irradiation in M. radiophilus is at least partly due to the presence of an efficient excision repair system.     

Impedance-based surveillance of transient permeability changes in coronary endothelial monolayers after exposure to ionizing radiation

The relative radiation sensitivities of the various compartments of the heart are poorly characterized. Cardiac fibrosis is a common side effect of radiotherapy, suggesting that endothelial barrier function is an important factor in radiation-induced pathology. We employed Electric Cell Substrate Impedance Sensing (ECIS) to assess cytoskeletal rearrangement, permeability changes and endothelial barrier function changes in response to radiation in studies of human coronary arterial endothelial cells (HCAECs). A 5-Gy dose of γ radiation resulted in a significant sixfold transient decrease in transmonolayer resistance 3 h postirradiation (P = 0.001). This decrease in resistance coincided with changes in fluorescent tracer flux (P = 0.05) and display of an actin bundling phenotype. After irradiation, decreases in wound healing (P = 0.03) and micromotion within the monolayer (P = 0.02) were also observed. Time-lapse video studies confirmed that the monolayer is dynamic and showed that cells are extruded from the monolayer at a higher frequency after irradiation. These findings suggest that perturbed endothelial barrier function in the heart can occur at lower doses of γ radiation than previously reported.     

The individual prognosis of the gravity and of the outcome of acute radiation disease based on immunological indexes

The information significance of the immunological indexes for the prognosis of gravity of course and of outcome of an acute radiation disease for the people after the exposure of ionizing radiation in clinically significant doses is studied. The value of indexes of the C-reactive protein contents, of the complement contents and of the titer of haemagglutinins in serum of a blood of 147 patients damaged at Chernobyl NPP accident as a result of external radiation gamma-exposure in combination with internal irradiation from the incorporation in an organism predominantly beta-emitting radionuclides were compared to the weight of acute radiation disease and its outcome (survival or loss). Was determined, that indexes of the contents of C-reactive protein in a peripheral blood during primary reactions on the irradiation (1-2 day after irradiation) and in latent period of disease (3-9 day after irradiation), and also titer of a complement on 3-9 day after irradiation can serve a source of information for the prognosis of probable gravity of a radiation injury and its outcome at irradiation of the man in clinically significant doses.