Plutonium transfer to wildlife at legacy sites

When internalized within an organism’s body, plutonium (Pu) can be important in dose calculation due to its relatively high-energy alpha emissions (~5-6 MeV). In this paper we quantify transfer of Pu to a range of wildlife types at legacy nuclear weapons sites and evaluate the importance of body tissue Pu distribution in the transfer of Pu through the food chain. The paper presents new data from Maralinga, Australia, as well as past data from terrestrial and marine settings of the US nuclear research program

Quantifiable Biomarkers of Normal Aging in the Japanese Medaka Fish (Oryzias latipes)

BACKGROUND: Small laboratory fish share many anatomical and histological characteristics with other vertebrates, yet can be maintained in large numbers at low cost for lifetime studies. Here we characterize biomarkers associated with normal aging in the Japanese medaka (Oryzias latipes), a species that has been widely used in toxicology studies and has potential utility as a model organism for experimental aging research. PRINCIPAL FINDINGS: The median lifespan of medaka was approximately 22 months under laboratory conditions. We performed quantitative histological analysis of tissues from age-grouped individuals representing young adults (6 months old), mature adults (16 months old), and adults that had survived beyond the median lifespan (24 months). Livers of 24-month old individuals showed extensive morphologic changes, including spongiosis hepatis, steatosis, ballooning degeneration, inflammation, and nuclear pyknosis. There were also phagolysosomes, vacuoles, and residual bodies in parenchymal cells and congestion of sinusoidal vessels. Livers of aged individuals were characterized by increases in lipofuscin deposits and in the number of TUNEL-positive apoptotic cells. Some of these degenerative characteristics were seen, to a lesser extent, in the livers of 16-month old individuals, but not in 6-month old individuals. The basal layer of the dermis showed an age-dependent decline in the number of dividing cells and an increase in senescence-associated β-galactosidase. The hearts of aged individuals were characterized by fibrosis and lipofuscin deposition. There was also a loss of pigmented cells from the retinal epithelium. By contrast, age-associated changes were not apparent in skeletal muscle, the ocular lens, or the brain. SIGNIFICANCE: The results provide a set of markers that can be used to trace the process of normal tissue aging in medaka and to evaluate the effect of environmental stressors

Neurocytotoxic effects of iron-ions on the developing brain measured in vivo using medaka (Oryzias latipes), a vertebrate model

Purpose: Exposure to heavy-ion radiation is considered a critical health risk on long-term space missions. The developing central nervous system (CNS) is a highly radiosensitive tissue; however, the biological effects of heavy-ion radiation, which are greater than those of low-linear energy transfer (LET) radiation, are not well studied, especially in vivo in intact organisms. Here, we examined the effects of iron-ions on the developing CNS using vertebrate organism, fish embryos of medaka (Oryzias latipes)

Whole-organism concentration ratios for plutonium in wildlife from past US nuclear research data

Whole-organism concentration ratios (CRwo-media) for plutonium (Pu) in wildlife were calculated using data from the broad range of organism types and environmental settings of the US nuclear research program. Original sources included site-specific reports and scientific journal articles typically from 1960s to 80s research. Most of the calculated CRwo-media values are new to existing data sets, and, for some wildlife categories, serve to fill gaps or add to sparse data including those for terrestrial reptile; freshwater bird, crustacean and zooplankton; and marine crustacean and zooplankton. Ratios of Pu concentration in the whole-organism to that in specific tissues and organs are provided here for a range of freshwater and marine fish. The CRwo-media values in fish living in liquid discharge ponds were two orders of magnitude higher than those for similar species living in lakes receiving Pu from atmospheric fallout, suggesting the physico-chemical form of the source Pu can dominate over other factors related to transfer, such as organism size and feeding behavior. Small rodent data indicated one to two order of magnitude increases when carcass, pelt, and gastrointestinal tract were included together in the whole-organism calculation compared to that for carcass alone. Only 4% of Pu resided in the carcass of small rodents compared to 75% in the gastrointestinal tract and 21% in the pelt. © 2012, Elsevier Ltd

Plutonium uptake in biota at former nuclear sites

Plutonium (Pu) is of ongoing interest as worldwide inventories continue to increase and plans for permanent storage of Pu wastes have stalled in many countries leaving large amounts in temporary storage. Pu also remains as environmental contamination at various locations due to: accidents (e.g., Chernobyl, UKR; Thule, GRL); research and processing releases (e.g., Los Alamos, USA, Mayak, RUS); and former weapons testing (e.g., Nevada Test Site, USA; Semipalatinsk, KAZ; and Maralinga, AUS). We assessed the availability and uptake of Pu in a range of wildlife types at legacy sites with the focus on new data from outside of the remediation zone at the former Taranaki site, Maralinga, South Australia. Of key interest are the uptake and biokinetics of Pu in mammals, particularly from environmental exposure to the undetonated Pu-oxide forms at Taranaki that are representative of much of the worldwide inventory. Our results confirm that environmentally dispersed Pu can remain accessible for uptake by biota over decadal time scales. For example, after more than 50 years since deposition at Taranaki, 62% of Pu has remained in the 0-2 cm surface layer, and nearly 100% in the 0-10 cm of soil depths. Although a small fraction of the Pu is migrating downward at —0.2 cm per year, it appears that most Pu will continue to remain accessible into the future for plants and animals that inhabit the surface, or shallow soil layers. The uptake of Pu into terrestrial animals occurs mainly by inhalation and ingestion, and can be persistent over time as indicated by constant uptake rates for mammals, and a potential increase for reptiles, in data spanning 30 years. The rates of soil-to-animal transfer at Taranaki, align well with those from similar sites where undetonated Pu was tested (e.g., Nevada Test Site, US). However, the uptake values at these sites are lower than general world-wide values, likely due to the presence of less-absorbable forms of Pu. The importance of the physico-chemical form of the Pu on uptake was also seen in data from fish exposed to more absorbable forms of Pu in liquid discharge ponds near processing facilities in the US. These fish had two orders of magnitude higher uptake values than those for similar species receiving Pu solely from atmospheric fallout. The physico-chemical form of the Pu can also influence how it is distributed among mammalian organs. The relatively insoluble forms at Taranaki, which include particulates, led to elevated concentrations of unabsorbed Pu in the lung, gastrointestinal tract, and adhered to skin/fur of mammals. This elevated Pu can provide a secondary source during human, and ecological, food-chain consumption. Of the Pu that was absorbed within the body, much higher accumulation was measured in the skeleton, and much lower in the liver, in mammals at Taranaki as compared with the standard model of 50% skeleton, and 30% liver (ICRP 1986). Our data provides specific quantification of Pu uptake rates in wildlife and the subsequent accumulation in various mammalian organs. These will aid future assessments of the Maralinga site, as well as more general evaluations related to the low-solubility forms of Pu that make up a large share of the worldwide inventory

Sister chromatid exchanges occur in G2-irradiated cells

DNA double-strand breaks (DSBs) are arguably the most important lesions induced by ionizing radiation (IR) since unrepaired or misrepaired DSBs can lead to chromosomal aberrations and cell death. The two major pathways to repair IR-induced DSBs are non-homologous end-joining (NHEJ) and homologous recombination (HR). Perhaps surprisingly, NHEJ represents the predominant pathway in the G1 and G2 phases of the cell cycle, but HR also contributes and repairs a subset of IR-induced DSBs in G2. Following S-phase-dependent genotoxins, HR events give rise to sister chromatid exchanges (SCEs), which can be detected cytogenetically in mitosis. Here, we describe that HR occurring in G2-irradiated cells also generates SCEs in ∼50% of HR events. Since HR of IR-induced DSBs in G2 is a slow process, SCE formation in G2-irradiated cells requires several hours. During this time, irradiated S-phase cells can also reach mitosis, which has contributed to the widely held belief that SCEs form only during S phase. We describe procedures to measure SCEs exclusively in G2-irradiated cells and provide evidence that following IR cells do not need to progress through S phase in order to form SCEs

PKC signaling prevents irradiation-induced apoptosis of primary human fibroblasts

Primary cells respond to irradiation by activation of the DNA damage response and cell cycle arrest, which eventually leads to senescence or apoptosis. It is not clear in detail which signaling pathways or networks regulate the induction of either apoptosis or senescence. Primary human fibroblasts are able to withstand high doses of irradiation and to prevent irradiation-induced apoptosis. However, the underlying regulatory basis for this phenotype is not well understood. Here, a kinetic network analysis based on reverse phase protein arrays (RPPAs) in combination with extensive western blot and cell culture analyses was employed to decipher the cytoplasmic and nuclear signaling networks and to identify possible antiapoptotic pathways. This analysis identified activation of known DNA damage response pathways (e.g., phosphorylation of MKK3/6, p38, MK2, Hsp27, p53 and Chk1) as well as of prosurvival (e.g., MEK-ERK, cAMP response element-binding protein (CREB), protein kinase C (PKC)) and antiapoptotic markers (e.g., Bad, Bcl-2). Interestingly, PKC family members were activated early upon irradiation, suggesting a regulatory function in the ionizing radiation (IR) response of these cells. Inhibition or downregulation of PKC in primary human fibroblasts caused IR-dependent downregulation of the identified prosurvival (CREB phosphorylation) and antiapoptotic (Bad phosphorylation, Bcl-2) markers and thus lead to a proliferation stop and to apoptosis. Taken together, our analysis suggests that cytoplasmic PKC signaling conditions IR-stressed MRC-5 and IMR-90 cells to prevent irradiation-induced apoptosis. These findings contribute to the understanding of the cellular and nuclear IR response and may thus eventually improve the efficacy of radiotherapy and help overcome tumor radioresistance

Assessing the risk of second malignancies after modern radiotherapy

Recent advances in radiotherapy have enabled the use of different types of particles, such as protons and heavy ions, as well as refinements to the treatment of tumours with standard sources (photons). However, the risk of second cancers arising in long-term survivors continues to be a problem. The long-term risks from treatments such as particle therapy have not yet been determined and are unlikely to become apparent for many years. Therefore, there is a need to develop risk assessments based on our current knowledge of radiation-induced carcinogenesis