Effects of a perfluorochemical emulsion on the response of BA1112 rat rhabdomyosarcomas to continuous low-dose-rate irradiation

The effects of the combination of a perfluorochemical emulsion (Fluosol DA, 20%) and carbogen (95% O2, 5% CO2) on the response of BA1112 rat rhabdomyosarcomas to continuous low-dose-rate irradiation were examined. Tumors were irradiated locally in unrestrained, unanesthetized rats at a dose rate of 0.98 Gy/h, using a specially designed 241Am irradiator system. Cell survival was measured using a colony formation assay. The tumor cell survival curves were fitted to linear relationships of the form ln S = - alpha D, where alpha for air-breathing rats was 0.104 +/- 0.005 Gy-1, as compared to 0.137 +/- 0.009 Gy-1 for rats treated with Fluosol plus carbogen. The increase in the slope of the survival curve produced by the treatment with Fluosol and carbogen was highly significant with a P value of 0.0015. The radiosensitization factor for the combination of Fluosol/carbogen plus continuous low-dose-rate irradiation was 1.32 +/- 0.11. Slightly less radiosensitization was observed with continuous low-dose-rate irradiation than in previous experiments using acute high-dose-rate irradiation. The diminished sensitization with Fluosol/carbogen during continuous low-dose-rate irradiation probably reflects the intrinsically lower oxygen enhancement ratio (OER) of low-dose/low-dose-rate irradiation, reoxygenation of the tumors during the prolonged treatment times used for continuous low-dose-rate irradiation, and the decrease in the levels of circulating perfluorochemicals during the 30-h irradiations. More importantly, the significant level of radiosensitization observed in the experiments with continuous low-dose-rate irradiation suggests that hypoxic cells persist in BA1112 tumors during continuous low-dose-rate irradiations and that the response of these tumors to continuous low-dose-rate irradiation can be improved by adjunctive treatments which oxygenate these radioresistant hypoxic tumor cells.     

Effects of Continuous Low Dose-Rate Irradiation: Computer Simulations

Abstract. The effects of continuous low dose-rate irradiation are studied with a computer model that incorporates cell kinetics and the accumulation and repair of radiation damage. This theoretical approach independently explores the effects on survival curves of a phase block, inherited damage and proliferation by dying cells. the computer model is a Monte Carlo simulation which follows the evolution in time of the family trees of a growing cell population under continuous irradiation. the model uses as input the measured phase-specific survival curves for acute exposures and the cell kinetic parameters to generate survival curves for continous low dose-rate irradiations. Cell survival curves for Chinese hamster lung cells (V79) for dose rates ranging from 15 to 500 cGy/h have been generated using various model assumptions. the model shows that for these cells a G₂ block will maximize cell killing for an optimum dose rate near 75 cGy/h. the effect on survival curves of inherited damage, as well as that of the proliferation by dying cells, is shown to increase monotonically with decreasing dose rates, and to be quite large at low dose rates.     

Habitat selection of riparian birds at restoration sites along the Trinity River,California

Riparian habitats in the western United States are imperiled, yet they support the highest bird diversity in arid regions, making them a conservation priority. Riparian restoration efforts can be enhanced by information on species response to variation in habitat features. We examined the habitat selection of four riparian birds known as management indicators at restoration and reference sites along the Trinity River, California. We compared vegetation structure and composition at nest sites, territories, and random points to quantify used versus available habitat from 2012 to 2015. Vegetation in focal species' territories differed between site types, and from available habitat, indicating nonrandom site choice. Birds selected aspects of more structurally complex habitats, such as greater canopy cover, canopy height, and tree species richness. Yellow‐breasted Chats preferred greater shrub cover, and Yellow Warblers preferred greater cover by non‐native Himalayan blackberry. Territory preferences on restoration sites were often a subset of those on reference sites. One exception was canopy height, which was taller on restoration site territories than random points for all species, suggesting that birds preferentially used patches of remnant habitat. Few variables were significant in nest site selection. Restoration plantings along the Trinity River were only 3–10 years old during this study, and have not developed many of the characteristics of mature riparian habitat preferred by birds, but may improve in habitat value over time. Understanding habitat selection is especially important in recently human‐modified environments, where indirect cues used to assess habitat quality may become disassociated from actual habitat quality, potentially creating ecological traps.     

Preclinical studies of porfiromycin as an adjunct to radiotherapy

The bioreductive alkylating agent porfiromycin (POR) is more toxic to EMT6 cells that are hypoxic at the time of treatment than to aerobic cells. The toxicity of POR to hypoxic EMT6 cells in vitro was similar to that of mitomycin C (MC): the aerobic toxicity of POR was considerably less than that of MC. Treatment of cells in vitro with POR before and during irradiation did not sensitize either hypoxic or aerobic cells to X rays; instead, only additive cytotoxicity was produced. In contrast, treatment of solid EMT6 tumors in vivo with POR plus radiation produced supra-additive cytotoxicity, as assessed by analyses of the complete dose-response curves for the killing of tumor cells by radiation alone or by POR alone. The supra-additivity of the combination regimens appeared to reflect the preferential killing by each agent of those tumor cells which were in an environment conferring resistance to the other agent. In contrast, combinations of POR and X rays produced only additive cytotoxicities to marrow CFU-GM. Supra-additive antineoplastic effects were obtained at doses of POR which produced little hematologic or other host toxicity. The complementary cytotoxicities of radiation and POR to cells in different microenvironments in solid tumors and the absence of a similar effect in normal tissue make optimized regimens combining radiotherapy and POR unusually promising for the treatment of solid tumors.     

Effects of continuous low dose-rate irradiation: computer simulations

The effects of continuous low dose-rate irradiation are studied with a computer model that incorporates cell kinetics and the accumulation and repair of radiation damage. This theoretical approach independently explores the effects on survival curves of a phase block, inherited damage and proliferation by dying cells. The computer model is a Monte Carlo simulation which follows the evolution in time of the family trees of a growing cell population under continuous irradiation. The model uses as input the measured phase-specific survival curves for acute exposures and the cell kinetic parameters to generate survival curves for continuous low dose-rate irradiations. Cell survival curves for Chinese hamster lung cells (V79) for dose rates ranging from 15 to 500 cGy/h have been generated using various model assumptions. The model shows that for these cells a G2 block will maximize cell killing for an optimum dose rate near 75 cGy/h. The effect on survival curves of inherited damage, as well as that of the proliferation by dying cells, is shown to increase monotonically with decreasing dose rates, and to be quite large at low dose rates.     

The Energetic Value of Land-Based Foods in Western Hudson Bay and Their Potential to Alleviate Energy Deficits of Starving Adult Male Polar Bears

Climate change is predicted to expand the ice-free season in western Hudson Bay and when it grows to 180 days, 28–48% of adult male polar bears are projected to starve unless nutritional deficits can be offset by foods consumed on land. We updated a dynamic energy budget model developed by Molnar et al. to allow influx of additional energy from novel terrestrial foods (lesser snow geese, eggs, caribou) that polar bears currently consume as part of a mixed diet while on land. We calculated the units of each prey, alone and in combination, needed to alleviate these lethal energy deficits under conditions of resting or limited movement (2 km d^-1) prior to starvation. We further considered the total energy available from each sex and age class of each animal prey over the period they would overlap land-bound polar bears and calculated the maximum number of starving adult males that could be sustained on each food during the ice-free season. Our results suggest that the net energy from land-based food, after subtracting costs of limited movement to obtain it, could eliminate all projected nutritional deficits of starving adult male polar bears and likely other demographic groups as well. The hunting tactics employed, success rates as well as behavior and abundance of each prey will determine the realized energetic values for individual polar bears. Although climate change may cause a phenological mismatch between polar bears and their historical ice-based prey, it may simultaneously yield a new match with certain land-based foods. If polar bears can transition their foraging behavior to effectively exploit these resources, predictions for starvation-related mortality may be overestimated for western Hudson Bay. We also discuss potential complications with stable-carbon isotope studies to evaluate utilization of land-based foods by polar bears including metabolic effects of capture-related stress and consuming a mixed diet.     

The early bear gets the goose: climate change,polar bears and lesser snow geese in western Hudson Bay

As climate change advances the date of spring breakup in Hudson Bay, polar bears are coming ashore earlier. Since they would have lost some of their opportunities to hunt ringed seals from a sea ice platform, they may be deficient in energy. Subadult polar bears appear to come ashore before more mature individuals and the earliest subadults are beginning to overlap the nesting period of the large colony of snow geese also occupying the Cape Churchill Peninsula. The eggs these bears are known to eat could make up some of their energy shortfall. The earlier these eggs are consumed during the snow goose nesting period, the greater would be the energy that is available. Recent studies have shown that the annual survival rate for subadult bears declined in contrast to that of prime aged individuals. If this reduction in survival is related to an increasing energy deficit, as suggested by some, the consumption of goose eggs may reverse the trend and help stabilize the population, at least for some period of time. The total number of polar bears that could benefit from this resource will depend on the increasing temporal overlap with the nesting period and on the foraging behaviors of individuals eating the eggs. It is likely that other food sources will also have to play a role if the polar bears are to persist.