The DNA damage response to radiological imaging: from ROS and γH2AX foci induction to gene expression responses in vivo.

Candidate ionising radiation exposure biomarkers must be validated in humans exposed in vivo. Blood from patients undergoing positron emission tomography-computed tomography scan (PET-CT) and skeletal scintigraphy (scintigraphy) was drawn before (0 h) and after (2 h) the procedure for correlation analyses of the response of selected biomarkers with radiation dose and other available patient information. FDXR, CDKN1A, BBC3, GADD45A, XPC, and MDM2 expression was determined by qRT-PCR, DNA damage (γH2AX) by flow cytometry, and reactive oxygen species (ROS) levels by flow cytometry using the 2', 7'-dichlorofluorescein diacetate test in peripheral blood mononuclear cells (PBMC). For ROS experiments, 0- and 2-h samples were additionally exposed to UVA to determine whether diagnostic irradiation conditioned the response to further oxidative insult. With some exceptions, radiological imaging induced weak γH2AX foci, ROS and gene expression fold changes, the latter with good coherence across genes within a patient. Diagnostic imaging did not influence oxidative stress in PBMC successively exposed to UVA. Correlation analyses with patient characteristics led to low correlation coefficient values. γH2AX fold change, which correlated positively with gene expression, presented a weak positive correlation with injected activity, indicating a radiation-induced subtle increase in DNA damage and subsequent activation of the DNA damage response pathway. The exposure discrimination potential of these biomarkers in the absence of control samples as frequently demanded in radiological emergencies, was assessed using raw data. These results suggest that the variability of the response in heterogeneous populations might complicate identifying individuals exposed to low radiation doses.

Small is beautiful: low activity alpha and gamma sources for small-scale radiation protection research experiments.

PURPOSE: Uncertainties regarding the magnitude of health effects following exposure to low doses of ionizing radiation remain a matter of concern both for professionals and for the public. There is consensus within the international radiation research community that more research is required on biological effects of radiation doses below 100 mGy applied at low dose rates. Moreover, there is a demand for increasing education and training of future radiation researchers and regulators. Research, education and training is primarily carried out at universities but university-based radiation research is often hampered by limited access to radiation sources. The aim of the present report is to describe small and cost-effective low activity gamma and alpha sources that can easily be installed and used in university laboratories. METHODS AND RESULTS: A gamma radiation source was made from an euxenite-(Y) rock (Y,Ca,Ce,U,Th)(Nb,Ta,Ti)2O6) that was found in an abandoned mine in Sweden. It allows exposing cells grown in culture dishes to radiation at a dose rate of 50 µGy/h and lower. Three alpha sources were custom-made and yield a dose rate of 1 mGy/h each. The construction, dosimetry and cellular effects of the sources are described. CONCLUSIONS: We hope that the report will stimulate research and training activities in the low dose field by facilitating access to radiation sources.

Seasonal disconnect between streamflow and retention shapes riverine nitrogen export in the Willamette River Basin, Oregon.

Watershed nutrient balance studies traditionally focus on annual fluxes. In areas with strongly seasonal, Mediterranean-type climate regimes, riverine nutrient export may be greater during wet seasons when hydrologic forcing overwhelms or bypasses retention mechanisms. By combining data on riverine export with spatially detailed nutrient inputs, we examine how nitrogen (N) supply, retention, and streamflow shape annual and seasonal riverine N export in Oregon's Willamette River Basin (WRB). The WRB has pronounced dry summers and wet winters, and the distribution of farmland, cities and forests create significant spatial variations in N inputs. Local data on N inputs were coupled with streamflow and chemistry to calculate fractional N export for 22 WRB sub-watersheds in the mid-2000s. For the entire WRB, 78% of the N inputs came from agricultural activities, mainly as synthetic fertilizer (69%); the next largest inputs were deposition (10%), alder fixation (5%) and point sources (5%). Crop-specific estimates of fertilizer agreed with county fertilizer sales rates at the high end of extension recommendations. Fractional riverine N export (annual riverine N export / net watershed N input) averaged 38% of net inputs in WRB tributaries, greater than other regions of North America. Fall and winter together accounted for 60-90% of the riverine N export across all watersheds. Summer export was small but was greatest in the watersheds that receive seasonal snowmelt. Large wet season losses, when biotic sinks are less active, result in a relatively high proportion of N inputs exported in this region with a Mediterranean climate and high runoff.

A Nitrogen Physical Input-Output Model for Illinois.

Nitrogen (N) presents an important challenge for sustainability. Human intervention in the global nitrogen cycle has been pivotal in in providing goods and services to society. However, release of N beyond its intended societal use has many negative health and environmental consequences. Several systems modeling approaches have been developed to understand the trade-offs between the beneficial and harmful effects of N. These efforts include life cycle modeling, integrated management practices and sustainability metrics for individuals and communities. However, these approaches do not connect economic and ecological N flows in physical units throughout the system, which could better represent these trade-offs for decision-makers. Physical Input-Output Table (PIOT) based models present a viable complementary solution to overcome this limitation. We developed a N-PIOT for Illinois representing the interdependence of sectors in 2002, using N mass units. This allows studying the total N flow required to produce a certain amount of N in the final product. An Environmentally Extended Input Output (EEIO) based approach was used to connect the physical economic production to environmental losses; allowing quantification of total environmental impact to support agricultural production in Illinois. A bottom up approach was used to develop the N-PIOT using Material Flow Analysis (MFA) tracking N flows associated with top 3 commodities (Corn, Soybean and Wheat). These three commodities cover 99% of N fertilizer use in Illinois. The PIOT shows that of all the N inputs to corn production the state exported 68% of N embedded in useful products, 9% went to animal feed manufacturing and only 0.03% was consumed directly within the state. Approximately 35% of N input to soybean farming ended up in animal feed. Release of N to the environment was highest from corn farming, at about 21.8% of total N fertilizer inputs, followed by soybean (9.2%) and wheat farming (4.2%). The model also allowed the calculation of life cycle N use efficiency for N based on physical flows in the economy. Hence, PIOTs prove to be a viable tool for developing a holistic approach to manage disrupted biogeochemical cycles, since these provide a detailed insight into physical flows in economic systems and allow physical coupling with ecological N flows.

Linking dissolved and particulate phosphorus export in rivers draining California's Central Valley with anthropogenic sources at the regional scale.

Pollution of water resources by phosphorus (P) is a critical issue in regions with agricultural and urban development. In this study, we estimated P inputs from agricultural and urban sources in 24 catchments draining to the Central Valley in California and compared them with measured river P export to investigate hydrologic and anthropogenic factors affecting regional P retention and export. Using spatially explicit information on fertilizer use, livestock population, agricultural production, and human population, we calculated that net surface balances for anthropogenic P ranged from -12 to 648 kg P km yr in the early 2000s. Inorganic P fertilizer and manure P comprised the largest fraction of total input for all but two catchments. From 2000 to 2003, a median of 7% (range, -287 to 88%) of net annual anthropogenic P input was exported as total P (TP). Yields (kg P km yr) of dissolved inorganic P (DIP), dissolved organic P, particulate P, and TP were not significantly related to catchment-level, per area anthropogenic P input. However, there were significant relationships between mean annual P concentrations and P input from inorganic fertilizers and manure due to the concentration of agricultural land near catchment mouths and regional variation in runoff. Catchment-level P fertilizer and manure inputs explained 4 to 23% more variance in mean annual DIP and TP concentrations than percent of catchment area in agriculture. This study suggests that spatially explicit estimates of anthropogenic P input can help identify sources of multiple forms of P exported in rivers at management-relevant spatial scales.

Nitrous oxide emission from denitrification in stream and river networks.

Nitrous oxide (N(2)O) is a potent greenhouse gas that contributes to climate change and stratospheric ozone destruction. Anthropogenic nitrogen (N) loading to river networks is a potentially important source of N(2)O via microbial denitrification that converts N to N(2)O and dinitrogen (N(2)). The fraction of denitrified N that escapes as N(2)O rather than N(2) (i.e., the N(2)O yield) is an important determinant of how much N(2)O is produced by river networks, but little is known about the N(2)O yield in flowing waters. Here, we present the results of whole-stream (15)N-tracer additions conducted in 72 headwater streams draining multiple land-use types across the United States. We found that stream denitrification produces N(2)O at rates that increase with stream water nitrate (NO(3)(-)) concentrations, but that <1% of denitrified N is converted to N(2)O. Unlike some previous studies, we found no relationship between the N(2)O yield and stream water NO(3)(-). We suggest that increased stream NO(3)(-) loading stimulates denitrification and concomitant N(2)O production, but does not increase the N(2)O yield. In our study, most streams were sources of N(2)O to the atmosphere and the highest emission rates were observed in streams draining urban basins. Using a global river network model, we estimate that microbial N transformations (e.g., denitrification and nitrification) convert at least 0.68 Tg·y(-1) of anthropogenic N inputs to N(2)O in river networks, equivalent to 10% of the global anthropogenic N(2)O emission rate. This estimate of stream and river N(2)O emissions is three times greater than estimated by the Intergovernmental Panel on Climate Change.

Stream denitrification across biomes and its response to anthropogenic nitrate loading.

Anthropogenic addition of bioavailable nitrogen to the biosphere is increasing and terrestrial ecosystems are becoming increasingly nitrogen-saturated, causing more bioavailable nitrogen to enter groundwater and surface waters. Large-scale nitrogen budgets show that an average of about 20-25 per cent of the nitrogen added to the biosphere is exported from rivers to the ocean or inland basins, indicating that substantial sinks for nitrogen must exist in the landscape. Streams and rivers may themselves be important sinks for bioavailable nitrogen owing to their hydrological connections with terrestrial systems, high rates of biological activity, and streambed sediment environments that favour microbial denitrification. Here we present data from nitrogen stable isotope tracer experiments across 72 streams and 8 regions representing several biomes. We show that total biotic uptake and denitrification of nitrate increase with stream nitrate concentration, but that the efficiency of biotic uptake and denitrification declines as concentration increases, reducing the proportion of in-stream nitrate that is removed from transport. Our data suggest that the total uptake of nitrate is related to ecosystem photosynthesis and that denitrification is related to ecosystem respiration. In addition, we use a stream network model to demonstrate that excess nitrate in streams elicits a disproportionate increase in the fraction of nitrate that is exported to receiving waters and reduces the relative role of small versus large streams as nitrate sinks.