Responses of the beagle to protracted irradiation. I. Effect of total dose and dose rate

The effects of protracted exposure to 60Co gamma rays on survival and tumor induction in the beagle were investigated. Total accumulated doses of 450, 1050, 1500, and 3000 cGy were given at rates of 3.8, 7.5, 12.8, and 26.3 cGy/day. Hazard models were used to identify trends in mortality associated with radiation exposure. The probability of an acute death (related to hematopoietic aplasia) was positively associated with the total dose received and the rate at which the dose was delivered. Once an animal survived the initial hematopoietic effects of radiation exposure, the risk of death from causes other than cancer, while elevated, was far less responsive than the neoplastic end points. No relationship between tumor or chronic nontumor deaths and dose rate could be identified. However, survival curves for tumor mortality did separate into a pattern clearly dependent on the accumulated dose.     

The effect of the dose rate on the development of rat pups under chronic gamma irradiation]

Chronic exposure of rat pups to gamma radiation, during their intensive growth, at a dose rate of 0.01, 0.11 and 0.5 cGy/day did not affect their development throughout a two-month period of observation. At a dose rate of 12.9 cGy/day rat growth was inhibited during the first 15 days. With further exposure at the same dose rate (over a period of up to five months) the rate of rat pup growth was restored, which indicated the presence of adaptation processes.     

Membrane structure alterations in rat blood lymphocytes under external low dose rate gamma-radiation exposure

The influence of a 0.72 cGy/day dose rate of gamma-radiation on plasma membranes of peripheral blood lymphocytes of rats exposed to the doses of 1.5, 15, 30, 60 and 100 cGy was studied. Parameters characterizing the viscosity and the polarity of lipid bilayer and also an external membrane surface properties were examined using fluorescent probes pyrene and 1-anilinonaphthalene-8-sulfonate (ANS). Was shown the membrane structural parameters alterations after animal exposure to the doses of 1.5, 15, 60 and 100 cGy, being of a nonmonotonous nature as the dose accumulated. After exposure to the doses lower then than 30 cGy spectral changes were revealed not in each particular experiment that was probably caused by the individual peculiarities of radiation response development. After exposure to the doses higher than 30 cGy the changes were of reproducible character. After a 1.5 cGy dose a slight lipid bilayer polarity decrease and ANS binding parameter multidirectional changes were observed. After exposure to 15, 60 and to 100 cGy was shown polarity elevation and repartition of polar groups within the bilayer, the increase of viscosity of more polar membrane regions and also ANS fluorescence reduction mostly at the expense of quantum yield decrease. After the exposure of 60 cGy was observed a viscosity decrease in hydrophobic regions along with viscosity increase in more polar regions and after a 100 cGy dose accumulation an essential surface charge shift was found. Revealed alterations indicate the reorganization of external membrane surface and of intensification of oxidative processes in lipid bilayer.     

Genetic effects in the liquidators of consequences of Chernobyl Nuclear Power Plant accident

The purpose of the present research was the estimation of probable genetic consequences at the liquidators of the consequences of Chernobyl accident in 1986-1987. The research is made on two groups of the liquidators. The first group included the liquidators taking place on the account in the branch register and working now at the enterprises of a nuclear industry. The second group included 902 liquidators of consequences of Chernobyl accident in 1986 constantly living in the Ryazan area and which are taking place on permanent observation the account in regional hospital. For an estimation of probable genetic effects analyzed the data on frequency and outcomes pregnancy of the wives of the liquidators, on condition and on diseases of newborn, on switching intrauterine development defects (IDD). The analysis carried out depending on dozes of an irradiation: up to 5 cGy; 5-10 cGy and 10-25 cGy. Received materials testify, that at the liquidators, at a doze of an external irradiation 10-25 cGy, the determined effects--period long sterility, kept at a part them till 3 years come to light. The set of the received data, such as depending from the dose increase of frequency of spontaneous abortions and of inherent defects of development of newborn, the increase of frequency diseases of newborn and share newborn with low weight, allows to make a conclusion about an induction of genetic effects in sexual cells of the liquidators of consequences of Chernobyl accident at dozes of an external irradiation more than 10 cGy. Taking into account high biological efficiency of alpha-radiation (K = 20), and of beta-radiation (K = 2-4), the equivalent effective doze male gonads (testes) in 3-5 times is higher, than estimated only from external gamma-radiation.     

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.     

Response of primary human fibroblasts exposed to solar particle event protons

Solar particle events (SPEs) present a major radiation-related risk for manned exploratory missions in deep space. Within a short period the astronauts may absorb doses that engender acute effects, in addition to the risk of late effects, such as the induction of cancer. Using primary human cells, we studied clonogenic survival and the induction of neoplastic transformation after exposure to a worst case scenario SPE. We simulated such an SPE with monoenergetic protons (50, 100, 1000 MeV) delivered at a dose rate of 1.65 cGy min?1 in a dose range from 0 to 3 Gy. For comparison, we exposed the cells to a high dose rate of 33.3 cGy min?1. X rays (100 kVp, 8 mA, 1.7 mm Al filter) were used as a reference radiation. Overall, we observed a significant sparing effect of the SPE dose rate on cell survival. High-dose-rate protons were also more efficient in induction of transformation in the dose range below 30 cGy. However, as dose accumulated at high dose rate, the transformation levels declined, while at the SPE dose rate, the number of transformants continued to increase up to about 1 Gy. These findings suggest that considering dose-rate effects may be important in evaluating the biological effects of exposure to space radiation. Our analyses of the data based on particle fluence showed that lethality and transforming potential per particle clearly increased with increasing linear energy transfer (LET) and thus with the decreasing energy of protons. Further, we found that the biological response was determined not only by LET but also type of radiation, e.g. particles and photons. This suggests that using γ or X rays may not be ideal for assessing risk associated with SPE exposures.     

Transformation of C3H 10T1/2 cells with 4.3 MeV alpha particles at low doses: effects of single and fractionated doses.

Oncogenic transformation of C3H 10T1/2 cells was determined after exposure to graded doses of 4.3-MeV alpha particles LET = 101 keV/microns. The source of alpha particles was 244Cm and the irradiation was done in an irradiation chamber built for the purpose. Graded doses in the range of 0.2 to 300 cGy were studied with special emphasis on the low-dose region, with as many as seven points in the interval up to 10 cGy. The dose-effect relationship was a complex function. Transformation frequency increased with dose up to 2 cGy; it seemed to flatten at doses between 2 and 20 cGy but increased again at higher doses. A total of 21 cGy was delivered in a single dose or in 3 or 10 equal fractions at an interval of 1.5 h. An inverse dose-protraction effect of 1.4 was found with both fractionation schemes. Measurements of the mitotic index of the population immediately before the various fractions revealed a strong effect on the rate of cell division even after very low doses of radiation. Mitotic yield decreased markedly with the total dose delivered, and it was as low as 50% of the control value after 4.2 cGy and 20% after 14 cGy with both fractionation schemes.     

Split-dose exposures versus dual ion exposure in human cell neoplastic transformation

Since radiation fields of space contain many-fold more protons than high atomic number, high energy (HZE) particles, cells in astronaut crews will experience on average several proton hits before an HZE hit. Thus radiation regimes of proton exposure before HZE particle exposure simulate space radiation exposure, and measurement of the frequency of neoplastic transformation of human primary cells to anchorage-independent growth simulates an initial step in cancer induction. Although previous investigations indicated a synergistic increase in transformation yields in the cells exposed to protons followed by HZE particles, these experiments did not differentiate between the effect of splitting of the dose into two fractions and that of changing the ion beams. To test this, we irradiated cells with split doses of either protons or HZE particles, then measured clonogenic survival and neoplastic transformation, as measured by colony formation in semi-solid soft agar medium. The data show that the split dose of 20 cGy plus 20 cGy of either H or HZE ions gave about the same effect as the 40 cGy uninterrupted dose, quite different from the effect of the mixed ion beam H + HZE irradiation. We also asked if lower proton doses than 20 cGy followed 15 min later by 20 cGy of HZE ions gave greater than additive transformation frequencies. Substantial increases in transformation levels were observed for all proton doses tested, including 1 cGy. These results point to the signal importance of protons in affecting the effect of space radiation on human cells.     

Comparison of the possibilities of micronuclear and chromosomal aberration tests for evaluation of the effects of radiation of different intensities

The comparative evaluation of sensitivity and specificity of the micronucleus and chromosome aberration tests for human lymphocytes at the delayed terms after acute exposure to high-dose as well as during constant exposure to low-dose gamma-radiation has been done. Accordance between these tests registered only in the cases of acute radiation sickness of second and third degrees of severity (irradiation doses above 200 cGy). Unspecificity of micronucleus test for estimation of the radiation load under constant low-intensity irradiation was found.     

Differential modulation of specific gene expression following high- and low-LET radiations

Experiments were designed to examine the effects of radiation quality on specific gene expression within the first 3 h following radiation exposure in Syrian hamster embryo (SHE) cells. Preliminary work demonstrated the induction of c-fos and alpha-interferon genes following exposure to low-linear-energy-transfer (low-LET) radiations (X rays or gamma rays). More detailed experiments revealed induction of c-fos mRNA within the first 3 h following exposure to either X rays (75 cGy) or gamma rays (90 cGy). We could not detect induction of c-fos following exposure of SHE cells to fission-spectrum neutrons (high-LET) from the JANUS reactor administered at either high (12 cGy/min) or low (0.5 cGy/min) dose rates. Expression of alpha-interferon mRNA was similarly induced by low-LET radiations but only modestly by JANUS neutrons. The induction by gamma rays was dose-dependent, while induction by neutrons was specific for low doses and low dose rates. These experiments demonstrate the differential gene inductive response of cells following exposure to high- and low-LET radiations. These experiments suggest that these different qualities of ionizing radiation may have different mechanisms for inducing many of the cellular consequences of radiation exposure, such as cell survival and cell transformation.     

Experimental study of the radioprotective action of melanin on the somatic development during irradiation in the antenatal period of ontogenesis

Daily introduction per os of the exogenous melanin in a doze of weight of 10 mg/kg pregnant female rats Wistar eliminated the functional deficiency of somatic development revealed at posterity at chronic gamma-irradiation in a doze 1.00-1.25 Gy for all period of pregnancy. The irradiation or introduction melanin antenatal to a phase ontogenesis resulted in stimulation of the immune answer, which was determined at offspring on 3rd week after birth. On the basis of the received data it is concluded presence radioembryoprotective actions melanin in the relation embryotoxic effects of small dozes of ionizing radiation and its participation in regulation immunogenes.     

Differential expression of oxidative stress and extracellular matrix remodeling genes in low- or high-dose-rate photon-irradiated skin

Changes in the expression of genes implicated in oxidative stress and in extracellular matrix (ECM) remodeling and selected protein expression profiles in mouse skin were examined after exposure to low-dose-rate or high-dose-rate photon irradiation. ICR mice received whole-body γ rays to total doses of 0, 0.25, 0.5 and 1 Gy at dose rates of 50 cGy/h or 50 cGy/min. Skin tissues were harvested for characterization at 4 h after irradiation. For oxidative stress after low-dose-rate exposure, 0.25, 0.5 and 1 Gy significantly altered 27, 23 and 25 genes, respectively, among 84 genes assessed (P < 0.05). At doses as low as 0.25 Gy, many genes responsible for regulating the production of reactive oxygen species (ROS) were significantly altered, with changes >2-fold compared to 0 Gy. For an ECM profile, 18-20 out of 84 genes were significantly up- or downregulated after low-dose-rate exposure. After high-dose-rate irradiation, of 84 genes associated with oxidative stress, 16, 22 and 22 genes were significantly affected after 0.25, 0.5 and 1 Gy, respectively. Compared to low-dose-rate radiation, high-dose-rate exposure resulted in different ECM gene expression profiles. The most striking changes after low-dose-rate or high-dose-rate exposure on ECM profiles were on genes encoding matrix metalloproteinases (MMPs), e.g., Mmp2 and Mmp15 for low dose rate and Mmp9 and Mmp11 for high dose rate. Immunostaining for MMP-2 and MMP-9 proteins showed radiation dose rate-dependent differences. These data revealed that exposure to low total doses with low-dose-rate or high-dose-rate photon radiation induced oxidative stress and ECM-associated alterations in gene expression profiles. The expression of many genes was differentially regulated by different total dose and/or dose-rate regimens.     

Effect of low doses of ionizing irradiation on viability of cortical thymocytes

The cortical thymocytes of rats in whole organism, isolated lobes of thymus and cells suspension were exposed to ionizing radiation in a wide range of doses (0.1-200 cGy). In contrast to relatively high dose radiation (50-200 cGy), exposure to doses of 10 cGy resulted in cell death without DNA degradation. The level of doses lower than 10 cGy (0.5-5 cGy) induced thymocyte death which is independent of DNA degradation, RNA and protein synthesis. With decrease in radiation dose, the increase of latent period preceding cell death took place.     

Effects of chronic gamma radiation on populations of Ips (Coleoptera: Scolytidae) in trap logs

Abstract. 1. Population dynamics of Ips calligraphus and I. grandicollis (Coleoptera: Scolytidae) were studied in a forest exposed to high doses of gamma radiation.
2. Populations were replicated at eleven dose rates by using 'trap logs'.
3. Adult beetles did not avoid high radiation intensities and attacked all sites equally.
4. Utilization of the cambium-inner bark area varied from c. 2% at a dose rate of 2520 R/20 h day to 90% at dose rates of 63 and 105 R/20 h day.
5. Developmental success of the new brood was directly dependent on the dose rate, and developing progeny were often killed by accumulated exposure.
6. Larger, slower developing species of subcortical beetles were eliminated at dose levels that allowed successful development of the two species of Ips bark beetles.     

Reaction of posterity of two generations after exposure of pregnant Wistar rats to low dose irradiation during the period of fetus formation. Development of the first generation posterity

Whole-body single exposure of female Wistar rats to 0.25, 0.5 and 1 Gy of gamma-rays (dose rate of 0.03 cGy/s) on the 10th day of pregnancy (a period of formation of the reproductive system in fetus) was carried out. To study irradiation consequences on the antenatal and postnatal development of the progeny 220 females, 700 19-day-old fetuses and about 1100 young rats were examined. The antenatal development of the progeny of the first generation was significantly impaired after the exposure to 1 Gy. However even less radiation doses resulted in a pronounced tendency to higher rates of intrauterine death and a lower number of live fetuses. Significant deviatins in the postnatal development of the first generation progeny were found after the exposure to 0.5 Gy, although the exposure to 0.25 Gy led to a higher rate of postnatal death and a less number of newborns in the litter.     

Protective effects of <Emphasis Type="SmallCaps">l</Emphasis>-selenomethionine on space radiation induced changes in gene expression

Ionizing radiation can produce adverse biological effects in astronauts during space travel. Of particular concern are the types of radiation from highly energetic, heavy, charged particles known as HZE particles. The aims of our studies are to characterize HZE particle radiation induced biological effects and evaluate the effects of l-selenomethionine (SeM) on these adverse biological effects. In this study, microarray technology was used to measure HZE radiation induced changes in gene expression, as well as to evaluate modulation of these changes by SeM. Human thyroid epithelial cells (HTori-3) were irradiated (1 GeV/n iron ions) in the presence or in the absence of 5 μM SeM. At 6 h post-irradiation, all cells were harvested for RNA isolation. Gene Chip U133Av2 from Affymetrix was used for the analysis of gene expression, and ANOVA and EASE were used for a determination of the genes and biological processes whose differential expression is statistically significant. Results of this microarray study indicate that exposure to small doses of radiation from HZE particles, 10 and 20 cGy from iron ions, induces statistically significant differential expression of 196 and 610 genes, respectively. In the presence of SeM, differential expression of 77 out of 196 genes (exposure to 10 cGy) and 336 out of 610 genes (exposure to 20 cGy) is abolished. In the presence or in the absence of SeM, radiation from HZE particles induces differential expression of genes whose products have roles in the induction of G1/S arrest during the mitotic cell cycle, as well as heat shock proteins. Some of the genes, whose expressions were affected by radiation from HZE particles and were unchanged in irradiated cells treated with SeM, have been shown to have altered expression levels in cancer cells. The conclusions of this report are that radiation from HZE particles can induce differential expression of many genes, some of which are known to play roles in the same processes that have been shown to be activated in cells exposed to radiation from photons (like cell cycle arrest in G1/S), and that supplementation with SeM abolishes HZE particle-induced differential expression of many genes. Understanding the roles that these genes play in the radiation-induced transformation of cells may help to decipher the origins of radiation-induced cancer.     

Experimental study of the neuroprotective properties of the melanin in embryos irradiated during antenatal development

Daily introduction per os of the exogenous melanin in a doze of weight of 10 mg/kg pregnant female rats of line Wistar on a background continuous irradiations (dose rate of 2.6 mGy/h within 20 days of pregnancy) eliminated deficiency cognitive functions at posterity. On the basis of the received data it is concluded presence radioembryoprotective actions of melanin in the relation neuro embryotoxic effects of small dozes ionizing radiation. Taking into account small toxicity of melanin, the preparation can be perspective for practical application.     

Changes in superoxide production rate and in superoxide dismutase and glutathione peroxidase activities in subcellular organelles in mouse liver under exposure to low doses of low-intensity radiation

The functioning of the antioxidant system in mouse liver at increased stationary concentration of active oxygen species induced by whole-body chronic exposure of mice to gamma-irradiation (137Cs, 0.6 cGy/day, 9 days) was studied. Synchronous changes (growth with an extreme) in activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) are found that may be considered as evidence in favor of maintenance of regulatory links in the antioxidant system of liver. The superoxide production rate in microsomes and nuclei also changed with an extreme with the rise in accumulated radiation dose. In microsomes the superoxide production rate reached a maximum at lower doses than the activity of Cu,Zn-SOD did. In nuclei the increase in superoxide production rate was not compensated by the rise in Cu,Zn-SOD activity within the studied dose range. The findings indicate some imbalance between production and consumption of superoxide radicals in microsomes and nuclei; in mitochondria these processes are balanced, leading to more resistance to low-dose irradiation.