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Uranium in bone: metabolic and autoradiographic studies in the rat.

The distribution and retention of intravenously injected hexavalent uranium-233 in the skeleton of the female rat has been investigated using a variety of autoradiographic and radiochemical techniques. These showed that approximately one third of the injected uranium is deposited in the skeleton where it is retained with an initial biological half-time of approximately 40 days. The studies also showed that: 1 Uranium is initially deposited onto all types of bone surface, but preferentially onto those that are accreting. 2 Uranium is deposited in the calcifying zones of skeletal cartilage. 3 Bone accretion results in the burial of surface deposits of uranium. 4 Bone resorption causes the removal of uranium from surfaces. 5 Resorbed uranium is not retained by osteoclasts and macrophages in the bone marrow. 6 Uranium removed from bone surfaces enters the bloodstream where most is either redeposited in bone or excreted via the kidneys. 7 The recycling of resorbed uranium within the skeleton tends to produce a uniform level of uranium contamination throughout mineralized bone. These results are taken to indicate that uranium deposition in bone shares characteristics in common with both the 'volume-seeking radionuclides' typified by the alkaline earth elements and with the 'bone surface-seeking radionuclides' typified by plutonium.

Animals↗

A toxicological study of the pentasodium salt of puchel using CBA mice.

Animal experiments have suggested that Puchel, a lipophilic derivative of DTPA may be of use in removing plutonium from humans after an accidental intake. This study reports toxicological findings in mice. After the administration of Puchel, as single or repeated doses of the pentasodium salt, an LD50/ld value of 530 +/- 44 mg kg-1 was obtained.

Animals↗

Nurture with ionizing radiation: a provocative hypothesis.

Whole body exposure to low-dose ionizing radiation appears to decrease overall cancer incidence. The data come from at least eight large studies of populations exposed to various forms of radioactive material and from more limited studies of occupational and environmental exposures to plutonium, radium, and radon. Earlier experiments in animals strongly support the protective effect that is apparent in humans. Also, experimental reports from invertebrates kept in radiation-deficient conditions suggest that ionizing radiation is essential for optimal growth and development. The combined evidence points to the presence of no-adverse-effect thresholds and of hormesis or beneficial effects at doses below those thresholds. Furthermore, according to the geological record, the high background radiation under which life first evolved has progressively attenuated up to the present. Thus it is intriguing to postulate that modern humans may live under conditions of partial deficiency of ionizing radiation; low doses of ionizing radiation may likely function as inducers of repair and detoxification mechanisms, much as low-level antigenic challenges are responsible for enhanced immune competence. This hypothesis runs contrary to the prevailing consensus of regulatory default assumptions, which negate the possibility of no-effect thresholds for agents that are carcinogenic at certain levels of exposure. Still, those are dogmatic policy assumptions without scientific or even empirical justification, whereas the hypothesis advanced here has consistent observational and experimental support. The implication is that a partial deficiency of ionizing radiation could be remedied by a safe supplementation, possibly through dietary means. Dose-response data from studies of nuclear workers and populations subjected to unusual exposures suggest that safe supplementation with about 0.4 cGy/mo would be beneficial and conservative.

Animals↗

giant nuclei is essential in the cell cycle transition from meiosis to mitosis.

At the transition from meiosis to cleavage mitoses, Drosophila requires the cell cycle regulators encoded by the genes, giant nuclei (gnu), plutonium (plu) and pan gu (png). Embryos lacking Gnu protein undergo DNA replication and centrosome proliferation without chromosome condensation or mitotic segregation. We have identified the gnu gene encoding a novel phosphoprotein dephosphorylated by Protein phosphatase 1 at egg activation. Gnu is normally expressed in the nurse cells and oocyte of the ovary and is degraded during the embryonic cleavage mitoses. Ovarian death and sterility result from gnu gain of function. gnu function requires the activity of pan gu and plu.

Actins↗

PAN GU: a protein kinase that inhibits S phase and promotes mitosis in early Drosophila development.

Following completion of meiosis, DNA replication must be repressed until fertilization. In Drosophila, this replication block requires the products of the pan gu (png), plutonium (plu) and giant nuclei (gnu) genes. These genes also ensure that S phase oscillates with mitosis in the early division cycles of the embryo. We have identified the png gene and shown that it encodes a Ser/Thr protein kinase expressed only in ovaries and early embryos, and that the predicted extent of kinase activity in png mutants inversely correlates with the severity of the mutant phenotypes. The PLU and PNG proteins form a complex that has PNG-dependent kinase activity, and this activity is necessary for normal levels of mitotic cyclins. Our results reveal a novel protein kinase complex that controls S phase at the onset of development apparently by stabilizing mitotic cyclins.

Amino Acid Sequence↗

Effects of negative pions and neutrons on the growth of Vicia faba bean roots.

Vicia faba bean roots have been irratiated with neutrons of various energies and with negative pi-mesons, and the effect on the ten-day growth of the roots has been determened. The neutron irratiations were made in beams of 400 and 600 MeV maximum energy, as well as with neutrons from a plutonium-beryllium source (mean energy 4.4 MeV) and from a 14 MeV neutron generator. The bean roots have also been irradiated at various points along the depth-dose curve of negative pi-mesons, including the gegion where the pions annihilate on coming to rest. The results show a maximum relative biological effectiveness (RBE) of 3.7 for 50% reduction in ten days growth for stopped negative pions and values up to 3.3 for high-energy neutrons, compared to 5.5 for 14 MeV neutrons. The biological effectiveness of high-energy neutrons and stopped pions shows a more pronounced dependence on dose than does the effect with lower-energy neutrons.

Dose-Response Relationship, Radiation↗

A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Residual radioactivity in neutron-exposed objects and residual alpha radioactivity in black rain areas.

The residual Eu-142 radioactivity due to the atomic bomb explosion in 1945 was first found in 1976 by in-situ high resolution gamma-ray spectrometry at Hiroshima. Since then, various studies on this nuclide have continued not only in Hiroshima but also in Nagasaki and they have contributed to the reevaluation of the neutron dose due to the A-bombing. By radiochemical separation methods and alpha-ray spectrometry, rather high levels of plutonium were found in the surface soil and in the bottom sediment of water reservoir which were collected at "Black rain area" in Nagasaki. The U-234/U-238 activity ratios for the uranium leached with 0.1 HNO3 from the surface of soil samples were found to be relatively higher for the samples which were collected at "Black rain area" in Hiroshima.

Alpha Particles↗

The Techa River Cohort: study design and follow-up methods.

Residents living on the banks of the Techa River in the Southern Urals region of Russia were exposed to radioactive contamination from the Mayak plutonium production and separation facility that discharged liquid radioactive waste into this river. This paper describes the methods used to establish and follow the Extended Techa River Cohort (ETRC), which includes almost 30,000 people living along the Techa River who were exposed to a complex mixture of radionuclides, largely 90Sr and 137Cs. The system of regular follow-up allows ascertainment of vital status, cause of death and cancer incidence. With over 50 years of follow-up and over 50% deceased, the ETRC now provides a valuable opportunity to study a wide range of health effects, both early and late, associated with protracted internal and external radiation exposures. The wide range of doses allows analysis of the nature of the dose-response relationship based on internal comparisons. Other features of the cohort are the high proportion (40%) exposed under age 20, and the inclusion of both sexes. The limitations of the study include loss to follow-up due to difficulties in tracing some cohort members and migration and incomplete ascertainment of cause of death.

Adult↗

Protracted radiation exposure and cancer mortality in the Techa River Cohort.

In the 1950s many thousands of people living in rural villages on the Techa River received protracted internal and external exposures to ionizing radiation from the release of radioactive material from the Mayak plutonium production complex. The Extended Techa River Cohort includes 29,873 people born before 1950 who lived near the river sometime between 1950 and 1960. Vital status and cause of death are known for most cohort members. Individualized dose estimates have been computed using the Techa River Dosimetry System 2000. The analyses provide strong evidence of long-term carcinogenic effects of protracted low-dose-rate exposures; however, the risk estimates must be interpreted with caution because of uncertainties in the dose estimates. We provide preliminary radiation risk estimates for cancer mortality based on 1,842 solid cancer deaths (excluding bone cancer) and 61 deaths from leukemia. The excess relative risk per gray for solid cancer is 0.92 (95% CI 0.2; 1.7), while those for leukemia, including and excluding chronic lymphocytic leukemia, are 4.2 (CI 95% 1.2; 13) and 6.5 (CI 95% 1.8; 24), respectively. It is estimated that about 2.5% of the solid cancer deaths and 63% of the leukemia deaths are associated with the radiation exposure.

Cohort Studies↗

ROS effects on neurodegeneration in Alzheimer's disease and related disorders: on environmental stresses of ionizing radiation.

Neurodegenerative processes associated with Alzheimer's disease are complex and involve many CNS tissue types, structures and biochemical processes. Factors believed involved in these processes are generation of Reactive Oxygen Species (ROS), associated inflammatory responses, and the bio-molecular and genetic damage they produce. Since oxidative processes are essential to energy production, and to other biological functions, such as cell signaling, the process is not one of risk exposure, as for cigarettes and cancer, but one where normal physiological processes operate out of normal ranges and without adequate control. Thus, it is necessary to study the ambiphilicity that allows the same molecule (e.g., beta amyloid) to behave in contradictory ways depending upon the physiological microenvironment. To determine ways to study this in human populations we review evidence on the effects of an exogenous generator of ROS, ionizing radiation, in major population events with radionuclides (e.g., Hiroshima and Nagasaki; Chernobyl Reactor accident; environmental contamination in Chelyabinsk (South Urals) where plutonium was produced, and in the nuclear weapons test area in Semipalatinsk, Kazakhstan). The age evolution, and traits, of neurodegenerative processes in human populations in these areas, may help us understand how IR affects the CNS. After reviewing human population evidence, we propose a model of neurodegeneration based upon the complexity of CNS functions.

Alzheimer Disease↗

Influence of physicochemical characteristics of freshwater on artificial radioactivity content.

An intensive study was designed to determine the activity of different radionuclides in water, including strontium-90 (90Sr), cesium-134 (134Cs), cesium-137 (137Cs), plutonium-239-240 (239+240Pu), and tritium (3H). Activity levels detected were between 0.6 and 21.3 mBq/L for 90Sr; less than 0.5, 1.4, and 327 Bq/L for 134Cs, 137Cs, and 3H, respectively; and between 0.14 and 21 microBq/L for 239+240Pu. Other nonradioactive parameters were measured including pH; dry residue: conductivity; calcium concentration, [Ca++]; magnesium concentration, [Mg++]; potassium concentration, [K+]; iron(II) and (III) concentration, [Fe2+,3+]; and ammonium concentration [NH4+]. Only the aquifer corresponding to the refrigeration reservoir of the nuclear power plant of Almaraz (Extremadura, Spain) showed greater-than-average concentrations of 3H and 239+240Pu compared with those found in the remaining aquifers. The greater presence of dissolved Fe in the waters analyzed clearly indicated greater activity associated with 90Sr, 137Cs, and 239+240Pu in dissolution. In addition, the water samples that were highly mineralized aided the dissolution of 90Sr and (to a lesser extent) 137Cs and made dissolution of 239+240Pu more difficult.

Environmental Monitoring↗

New developments in therapeutic chelating agents as antidotes for metal poisoning.

An examination of the studies on therapeutic chelating agents that have been carried out during the last decade reveals that extensive efforts have been made to develop compounds superior to those previously available for the treatment of acute and chronic intoxication by many metals. These metals include primarily iron, plutonium, cadmium, lead, and arsenic, but also many other elements for which acute and chronic intoxication is less common. These studies have revealed the importance of several additional factors of importance in the design of such compounds and have led to many new compounds of considerable clinical promise. An additional development has been the introduction of previously developed chelating agents for use with certain metals on a broader scale.

Animals↗

Testicular atrophy in a mule deer population.

Monitoring mule deer (Odocoileus hemionus) on a former plutonium production site along the Columbia River at the Hanford Site, Washington (USA) revealed 27 (23%) of 116 adult males had unusually shaped, velvet-covered antlers and abnormally developed testicles. We captured 32 males to examine age-class differences and the ratio of affected to unaffected deer and determine whether affected testicles were atrophic or hypoplastic. We found testicular atrophy in most deer with velvet-covered antlers, primarily in animals older than 5 yr. Deer had marked to extreme stages of testicular atrophy, indicating permanent sterility. Decreased serum levels of testosterone and compensatory increased levels of luteininzing hormone and follicle stimulating hormone were detected in all affected males; thus, the gondopituitary hormonal pathway may have responded to abnormally low levels of testosterone in the affected animals. Brucella spp. antibodies in sera were not detected and 9 (90%) of 10 affected animals were seropositive for epizootic hemorrhagic disease virus (EHDV-2) and bluetongue virus (BTV-11) as compared to 12 (63%) of 19 unaffected animals; however, signs of other infectious diseases were not observed. Testicular degeneration generally exceeded that observed with nutritional disorders and poisons in domestic species. Also, severity of the atrophy and apparent lack of other affected tissues suggested that radiation may not be responsible. Testicular atrophy in mule deer has been reported elsewhere; however, neither prevalence has been as high nor or occurrence as well confined to a specific geographical area, as that observed at the Hanford Site. Furthermore, no physiological or age-related influences were described. Documenting the status of such variables and examining their relationships to this phenomenon is a crucial step in understanding the reproductive capacity of a wild deer population.

Age Factors↗

Temporal change in microdosimetry to bone marrow and stromal progenitor cells from alpha-particle-emitting radionuclides incorporated in bone.

The microdistributions of the alpha-particle-emitting bone surface-seeking radionuclides (239)Pu, (241)Am and (233)U in the mouse femoral shaft have been studied using computer-based image analysis of neutron-induced and alpha-particle track autoradiographs, prepared from femora of CBA/H mice which had been injected with 40 kBq kg(-1) of radionuclide (as citrate solution) at times from 1 to 448 days previously. Employing dosimetric methods, radiation dose rates and cumulative radiation doses to regions of the bone marrow thought to contain hemopoietic and stromal progenitor cells susceptible to neoplastic transformation to leukemia and osteosarcomas have been calculated. It has been shown that the three radionuclides differ in their relative deposition on the bone surfaces, and that patterns of changing redistribution with time are also varied. For stromal progenitor cells, which are thought to be targets for induction of osteosarcoma and are found in proximity to the bone surfaces, cumulative doses showed the trend (239)Pu > (241)Am > (233)U, correlating well with incidences of osteosarcoma observed in mice. Cumulative doses to the primitive hemopoietic stem cells, concentrated in the central marrow and thought to be susceptible to neoplastic transformation to myeloid leukemia, were considerably lower and also showed the trend plutonium > americium > uranium.

Alpha Particles↗

Alpha-particle doses to cells of the bone remodeling cycle from alpha-particle-emitting bone-seekers: indications of an antiresorptive effect of actinides.

There are indications that alpha-particle-emitting bone-seekers such as plutonium or americium could enhance bone mass by suppressing bone resorption. To assess this possibility, this study calculates doses from alpha-particle emitters to the cells involved in trabecular bone turnover. Alpha-particle energy deposition in tissue from a bone surface source was calculated by Monte Carlo modeling. This was combined with bone surface cellular geometry to yield dose rates to cells during the remodeling cycle. Bone-resorbing osteoclasts receive on average 50 times the dose rate that bone-forming osteoblasts receive. Newly formed bone shields osteoblasts from alpha particles emitted by the buried deposit of alpha-particle emitters. However, at alpha-particle bone-seeking radionuclide intakes known to cause changes in remodeling (about 3700 Bq/kg body weight), the alpha-particle dose to osteoclasts corresponds to an extremely low rate of cell traversals (0.07% per cycle). It is therefore unlikely that perturbation of bone remodeling by alpha-particle bone-seeking radionuclides is directly caused by alpha-particle traversals of remodeling cells; some other indirect mechanism might be involved.

Actinoid Series Elements↗

Birds as objects in bioindication of radioactive pollution.

This article is a review the recent results of research in the accumulation of natural and artificial radionuclides in birds from Russia (Adigea, Krasnodar, Rostov, Astrahan and Moscow regions, Novaya Zemlya isles), Ukraine, Vietnam, Poland, Ethiophia and Mongolia after global precipitation and local pollution, such as in the East-Urals radioactive region and radioactive zones after the Chernobyl accident. Resident birds reflect local level of radionuclide contamination. The 90Sr concentration in the food of the Pied Flycatcher had a tendency to increase in dependent of age. The Common Jay and the Mallard were the most contaminated with 137Cs in the Bryansk region. The total content of various radio-isotopes of plutonium in bird bones from Southwest Russia were hundred and thousand times more, than in Mongolia. Activity levels in specimens from Ethiopia bear record to Ethiopia can notbe a "pure" control site in radioecological research and radioactive background since it does not significantly differ from Turkmenia and Mongolia.

Animals↗

[Chromosomal instability in offspring of voles in unfavorable radiation zones].

A high frequency of cells having chromosomal aberrations was shown to be preserved in the first generation of laboratory offspring of common voles, whose ancestors were captured near the East Ural radioactive track (EURT). In F2 and F3, a decrease in frequency was observed. Most likely, the cytogenetic effects observed were caused by environmental contamination with plutonium in the locality of capture. An increased chromosomal instability observed in the first laboratory generation of nonirradiated common voles was caused by reversible modifications in the expression of mutator genes inherited from parents exposed to alpha-irradiation rather than by classic mutations occurred in specific loci.

Animals↗

The management of radioactive wastes resulting from emergency situations on land and sea.

The term 'emergency' applies to unplanned events that have generated, or had the potential to generate, radioactive wastes that could not be handled locally. Reports of past emergencies form the basis for discussion of future trends in emergency situations, the factors that influence waste management, the technology of waste management and personnel requirements. The number of past emergencies has been small and these have not increased the volume of radioactive wastes significantly. The majority of future emergencies are likely to be associated with reactors as they have been in the past. Little change in the nature of the waste is expected, although the greater use of separated plutonium may create some new problems. The factors that influence emergency waste management fall into two categories, those that are concerned with the location of the emergency event, and those concerned with the characteristics of the wastes. As in the past, it can be expected that in most emergencies proven waste management techniques will be adapted to suit the local circumstances but there is a need for simpler and more economic methods. Trained personnel and comprehensive planning are cited as key factors in successful waste management operations.

Accidents↗