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Anthropogenic impacts can lead to increased temperatures in freshwater environments through thermal effluent and climate change. Thermal preference of aquatic organisms can be modulated by abiotic and biotic factors including environmental temperature. Whether increased temperature during embryogenesis can lead to long-term alterations in thermal preference has not been explicitly tested in native freshwater species. Lake (Coregonus clupeaformis) and round (Prosopium cylindraceum) whitefish were incubated at natural and elevated temperatures until hatching, following which, all groups were moved to common garden conditions (15°C) during the post-hatching stage. Temperature preference was determined at 8 (Lake whitefish only) and 12-months of age (both species), using a shuttlebox system. Round whitefish preferred a cooler temperature when incubated at 2°C and 6°C compared to 0.5°C. Lake whitefish had similar temperature preferences regardless of age, weight, and incubation temperature. These results reveal that temperature preference in freshwater fish can be programmed during early development, and that round whitefish may be more sensitive to incubation temperature. This study highlights the effects that small increases in temperature caused by anthropogenic impacts may have on cold-adapted freshwater fish.

Living systems have evolved in the presence of naturally occurring ionising radiation. REPAIR is a research project investigating the biological effects of sub-natural background radiation exposure in SNOLAB, a deep-underground laboratory. Biological systems are being cultured within a sub-background environment as well as two control locations (underground and surface). A comprehensive dosimetric analysis was performed. GEANT4 simulation was used to characterise the contribution from gamma, muons and neutrons. Additionally, dose rates from radon, 40K and 14C were calculated based on measured activity concentrations. The total absorbed dose rate in the sub-background environment was 27 times lower than the surface control, at 2.48 ± 0.20 nGy hr−1, including a >400-fold reduction in the high linear energy transfer components. This modelling quantitatively confirms that the environment within SNOLAB provides a substantially reduced background radiation dose rate, thereby setting the stage for future sub-background biological studies using a variety of model organisms.

We developed an incremental growth-at-temperature model to predict hatch timing for lake whitefish under varying incubation temperatures. The model extends earlier approaches by incorporating a temperature-dependence for development stage at hatching. Testing using experimentally reared embryos from Lakes Huron and Simcoe demonstrates improved predictive accuracy compared to previous models for asymmetrically varying thermal regimes that mimic aspects of those encountered under real-world conditions. The simple calibration of the model to different populations and its ability to predict observed phenomena such as thermally-induced mass hatching and hatching synchronization makes it a useful tool for the evaluation of thermal impacts from industrial discharges and climate change.

Advancements in medical technologies that utilize ionizing radiation have led to improved diagnosis and patient outcomes, however, the effect of ionizing radiation on the patient is still debated. ...

Nontargeted low-dose ionizing radiation has been proposed as a cancer therapeutic for several decades; however, questions remain about the duration of hematological changes and optimal dosing regimen. Early studies delivering fractionated low doses of radiation to patients with cancer used varying doses and schedules, which make it difficult to standardize a successful dose and scheduling system for widespread use. The aim of this phase 2 two-stage trial was to determine whether low-dose radiation therapy (LD-RT) reduced prostate-specific antigen (PSA) in patients with recurrent prostate cancer in efforts to delay initiation of conventional therapies that are known to decrease quality of life. The primary study outcome was reduction in PSA levels by at least 50%.Sixteen patients with recurrent prostate cancer were recruited and received 2 doses of 150 mGy of nontargeted radiation per week, for 5 consecutive weeks, with 15 participants completing the study.A maximal response of 40.5% decrease in PSA at 3 months was observed. A total of 8 participants remained off any additional interventions, of whom 3 had minor fluctuations in PSA for at least 1 year after treatment. The most common adverse event reported was mild fatigue during active treatment (n = 4), which did not persist in the follow-up period. No participants withdrew due to safety concerns or hematological abnormalities (ie, platelet ≤50 × 10Our study did not meet the primary objective; however, LD-RT may be a potential therapy for some patients with recurrent prostate cancer by stalling rising PSA. This study also demonstrates that low-dose radiation is well tolerated by participants with minimal toxicities and no change in quality of life.

Long-term temperature shifts associated with seasonal variability are common in temperate regions. However, these natural shifts could place significant strain on thermal stress responses of fishes when combined with mean increases in water temperatures predicted by climate change models. We examined the relationship between thermal acclimation, basal expression of heat shock protein (hsp) genes and the activation of the heat shock response (HSR) in lake whitefish (LWF; Coregonus clupeaformis), a cold water species of cultural and commercial significance. Juveniles were acclimated to either 6, 12, or 18°C water for several months prior to the quantification of hsp mRNA levels in the presence or absence of acute heat shock (HS). Acclimation to 18°C increased basal mRNA levels of hsp70 and hsp47, but not hsc70 or hsp90β in gill, liver and white muscle, while 6°C acclimation had no effect on basal hsp transcription. Fish in all acclimation groups were capable of eliciting a robust HSR following acute HS, as indicated by the upregulation of hsp70 and hsp47. An increase of only 2°C above the 18°C acclimation temperature was required to trigger these transcriptional changes, suggesting that the HSR may be frequently initiated in LWF populations living at mildly elevated temperatures. Collectively, these expression profiles show that environmental temperature influences both basal hsp levels and the HSR in LWF, and indicate that these fish may have a greater physiological and ecological susceptibility to elevated temperatures than to cooler temperatures.

Background: Space radiation is one of the principal environmental factors limiting the human tolerance for space travel, and therefore a primary risk in need of mitigation strategies to enable crewed exploration of the solar system. Methods: We summarize the current state of knowledge regarding potential means to reduce the biological effects of space radiation. New countermeasure strategies for exploration-class missions are proposed, based on recent advances in nutrition, pharmacologic, and immune science. Results: Radiation protection can be categorized into (1) exposure-limiting: shielding and mission duration; (2) countermeasures: radioprotectors, radiomodulators, radiomitigators, and immune-modulation, and; (3) treatment and supportive care for the effects of radiation. Vehicle and mission design can augment the overall exposure. Testing in terrestrial laboratories and earth-based exposure facilities, as well as on the International Space Station (ISS), has demonstrated that dietary and pharmacologic countermeasures can be safe and effective. Immune system modulators are less robustly tested but show promise. Therapies for radiation prodromal syndrome may include pharmacologic agents; and autologous marrow for acute radiation syndrome (ARS). Conclusions: Current radiation protection technology is not yet optimized, but nevertheless offers substantial protection to crews based on Lunar or Mars design reference missions. With additional research and human testing, the space radiation risk can be further mitigated to allow for long-duration exploration of the solar system.

Lake whitefish (Coregonus clupeaformis) embryos incubated at low temperatures have a longer incubation period and hatch at a significantly greater size than those incubated at warmer temperatures. We examined hatch timing and morphological characteristics for whitefish embryos reared under different constant and varying temperatures to determine whether the thermal dependence of hatching size reflects differences in their development stage. Our results show that lake whitefish embryos hatch at different temperature-dependent developmental stages, and this is the dominant factor affecting size-at-hatch. The term “heterograde” is proposed for the thermal dependence of hatching stage to differentiate it from hatching that occurs at a fixed developmental stage. A method to quantify this effect is given using a ratio that describes the difference in relative development at hatching between different viable constant incubation temperatures. Heterograde hatching is proposed as a possible mechanism to synchronize the timing of hatch to the break-up of winter ice cover despite variability in the date of spawning and in the onset of spring break-up.

McIntyre Powder (MP) is a finely ground aluminum powder that was used between 1943 and 1979 as a prophylaxis for silicosis. Silicosis is a chronic lung disease caused by the inhalation of crystalline silica dust and was prevalent in the Canadian mining industry during this time period. The McIntyre Research Foundation developed, patented, and produced the MP and distributed it to licensees in Canada, the United States, Mexico, Chile, Belgian Congo, and Western Australia. In the province of Ontario, Canada it is estimated that at least 27,500 miners between 1943 and 1979 were exposed to MP. The present study was undertaken to examine the chemical and physical characteristics of two variations of MP (light grey and black). Chemical analyses (using X-ray Fluorescence and Inductively Coupled Plasma approaches) indicate that the black MP contains significantly higher concentrations of aluminum and metal impurities than the light grey MP (p

Purpose: Diagnostic radiation is an important part of patient care in the Intensive Care Unit; however, there is little data on the acute effects of exposure to these doses. We investigated...

Ionizing radiation (IR) is known to cause fetal programming, but the physiological effects of low-dose IR are not fully understood. This study examined the effect of low (50 mGy) to non-lethal (300 and 1000 mGy) radiation exposure during late gestation on cardiac metabolism and oxidative stress in adult offspring. Pregnant C57BL/6J mice were exposed to 50, 300, or 1000 mGy of gamma radiation or Sham irradiation on gestational day 15. Sixteen weeks after birth, 18F-Fluorodeoxyglucose (FDG) uptake was examined in the offspring using Positron Emission Tomography imaging. Western blot was used to determine changes in oxidative stress, antioxidants, and insulin signaling related proteins. Male and female offspring from irradiated dams had lower body weights when compared to the Sham. 1000 mGy female offspring demonstrated a significant increase in 18F-FDG uptake, glycogen content, and oxidative stress. 300 and 1000 mGy female mice exhibited increased superoxide dismutase activity, decreased glutathione peroxidase activity, and decreased reduced/oxidized glutathione ratio. We conclude that non-lethal radiation during late gestation can alter glucose uptake and increase oxidative stress in female offspring. These data provide evidence that low doses of IR during the third trimester are not harmful but higher, non-lethal doses can alter cardiac metabolism later in life and sex may have a role in fetal programming.

We examined the impact of repeated thermal stress on the heat shock response (HSR) of thermally sensitive lake whitefish (Coregonus clupeaformis) embryos. Our treatments were designed to mimic temperature fluctuations in the vicinity of industrial thermal effluents. Embryos were either maintained at control temperatures (3 oC) or exposed to a repeated thermal stress (TS) of 3 or 6 oC above control temperature every 3 or 6 days throughout embryonic development. At 82 days post-fertilisation, repeated TS treatments were stopped and embryos received either a high level TS of 12, 15, or 18 oC above ambient temperature for 1 or 4 h, or no additional TS. These treatments were carried out after a 6 h recovery from the last repeated TS. Embryos in the no repeated TS group responded, as expected, with increases in hsp70 mRNA in response to 12, 15 and 18 oC high-level TS. However, exposure to repeated TS of 3 or 6 ⁰C every 6 days also resulted in a significant upregulation of hsp70 mRNA relative to the controls. Importantly, these repeated TS events and the associated elevations in hsp70 attenuated the upregulation of hsp70 in response to a 1 h, high-level TS of 12 oC above ambient, but not to either longer (4 h) or higher (15 or 18 oC) TS events. Conversely, hsp90α mRNA levels were not consistently elevated in the no repeated TS groups exposed to high-level TS. In some instances, hsp90α levels appeared to decrease in embryos exposed to repeated TS followed by a high-level TS. The observed attenuation of the HSR in lake whitefish embryos demonstrates that embryos of this species have plasticity in their HSR and repeated TS may protect against high-level TS, but the response differs based on repeated TS treatment, high-level TS temperature and duration, and the gene of interest.

Cells exposed to fast neutrons often exhibit a non-Poisson distribution of chromosome aberrations due to the high ionization density of the secondary reaction products. However, it is unknown whether lymphocytes exposed to californium-252 (252Cf) spectrum neutrons, of mean energy 2.1 MeV, demonstrate this same dispersion effect at low doses. Furthermore, there is no consensus regarding the relative biological effectiveness (RBE) of 252Cf neutrons. Dicentric and ring chromosome formations were assessed in human peripheral blood lymphocytes irradiated at doses of 12-135 mGy. The number of aberrations observed were tested for adherence to a Poisson distribution and the maximum low-dose relative biological effectiveness (RBEM) was also assessed. When 252Cf-irradiated lymphocytes were examined along with previously published cesium-137 (137Cs) data, RBEM values of 15.0 ± 2.2 and 25.7 ± 3.8 were found for the neutron-plus-photon and neutron-only dose components, respectively. Four of the five dose points were found to exhibit the expected, or close to the expected non-Poisson over-dispersion of aberrations. Thus, even at low doses of 252Cf fast neutrons, when sufficient lymphocyte nuclei are scored, chromosome aberration clustering can be observed.

Advancements in medical technologies that utilize ionizing radiation have led to improved diagnosis and patient outcomes, however, the effect of ionizing radiation on the patient is still debated. In the case of pregnancy, the potential effects are not only to the mother but also to the fetus. The aim of this study was to determine if exposure from ionizing radiation during pregnancy alters the development of the cardiovascular and respiratory system of the offspring.Pregnant C57Bl/6 mice were whole-body irradiated at gestational day 15 with a

Aging is associated with changes in regulation, particularly among diverse regulators in the brain. We assayed prominent regulatory elements in mouse brain to explore their relationship to one another, stress, and aging. Notably, unphosphorylated (activated) forkhead transcription factor 3a (uFOXO3a) expressed exponential decline congruent with increasing age-related mortality. Decline in uFOXO3a would impact homeostasis, aging rate, stress resistance, and mortality. We also examined other regulators associated with aging and FOXO3a: protein kinase B (PKB), the mechanistic target of rapamycin (mTOR), 70 kDa ribosomal S6 kinase (P70S6K), and 5’ AMP-activated protein kinase (AMPK). It would require powerful regulatory distortion, conflicting tradeoffs and/or significant damage to inflict exponential decline of a transcription factor as crucial as FOXO3a. No other regulator examined expressed an exponential pattern congruent with aging. PKB was strongly associated with decreases in uFOXO3a, but the aging pattern of PKB did not support a causal linkage. Although mTOR expressed a trend for age-related increase, this was not significant. We considered that the mTOR downstream element, P70S6K, might suppress FOXO3a, but remarkably, it expressed a strong positive association. The age-related pattern of AMPK was also incompatible. Literature suggested the immunological regulator NFĸB (nuclear factor kappa-light-chain-enhancer of activated B cells) increases with age and suppresses FOXO3a. This would inhibit apoptosis, autophagy, mitophagy, proteostasis, detoxification, antioxidants, chaperones, and DNA repair, thus exacerbating aging. We conclude that a key aspect of aging involves distortion of key regulators in the brain.

Thermal preferenda are largely defined by optimal growth temperature for a species and describe the range of temperatures an organism will occupy when given a choice. Assays for thermal preferenda require at least 24 hours, which includes a long acclimation to the tank, limits throughput and thus impacts replication in the study. Three different behavioral assay experimental designs were tested to determine the effect of tank acclimation and trial length (12:12, 0:12, 2:2; hours of tank acclimation: behavioral trial) on the temperature preference of juvenile lake whitefish, using a shuttle box system. Average temperature preferences for the 12:12, 0:12, and 2:2 experimental designs were 16.10 ± 1.07 °C, 16.02 ± 1.56 °C, 16.12 ± 1.59°C respectively, with no significant differences between the experimental designs (p= 0.9337). Ultimately, length of acclimation time and trial length had no significant impact, suggesting that all designs were equally useful for studies of temperature preference.

In order to facilitate direct testing of the biological effects of radon, we designed and constructed a 3.1 m3 radon chamber specifically for radon exposures to small animals. The chamber is designed to operate as a sealed enclosure with a controlled atmosphere containing a known concentration of radon and its radioactive decay products. Sensors for air flow rate, temperature, humidity, HEPA filter and differential pressure ensure an optimal environment for exposure subjects. The radon gas is supplied to the chamber from a generator containing Radium-226 in a dilute acid solution. Air containing radon can be pumped continuously using a constant flow rate to maintain a steady state supply. The source flow rate was partitioned to achieve a chamber concentration at 200 Bq/m3 (R2 = 0.9341) or 1000 Bq/m3 (R2 = 0.9715). Small particles are injected into the re-circulating air stream via a particle generator to provide condensation nuclei for attachment of radon decay products as they form in the chamber atmosphere. Particles measured at 0.3 μm, 0.5 μm and 5.0 μm averaged concentrations 5.7 ± 0.6 × 107/m3, 2.5 ± 0.7 × 107/m3 and 2.3 ± 2.4 × 103/m3, respectively. A desired Equilibrium Factor can easily be achieved by varying the air circulation rate through the chamber. The Equilibrium Factor ranged from 0.4 to 0.8 at 200 Bq/m3 and 0.5 to0.6 at 1000 Bq/m3. The chamber was designed to conduct short term exposures to assess the acute cellular changes induced by radon exposure. To our knowledge, this is currently the only radon chamber designed specifically to investigate environmentally relevant exposure time and doses of radon gas and decay products in small animal models.

Ionizing radiation exposure to the lens of the eye is a known cause of cataractogenesis. Administrative data from the Ontario Health Insurance Program was used to examine the association between low-dose radiation exposure from head CT scans and cataract extraction surgery for 16 million Ontarians over a 22-year period (1994-2015). Subjects were grouped based on the number of head CT scans they received, and a Cox proportional hazards analysis was used to determine if there was a correlation with cataract surgery. Covariates included in the analysis were age, sex, diabetes, hypertension and prior history of intraocular surgery. To account for the potentially long latency period between radiation exposure and cataract formation, the data were analyzed incorporating a 5- and 10-year lag between head CT scan exposure and cataract surgery. Both the 5- and 10-year lagged models followed a similar trend, where only the first three head CT scans significantly increased the risk of cataract surgery by 3-8%. Individuals receiving four or more head CT scans did not have an increased cataract risk and in several cases the risk was reduced. Overall, no positive dose-response relationship was seen between the number of head CT scans received and the risk of cataract surgery. Due to the nature of the data extracted from medical records, several uncertainties exist in the analysis related to dosimetry, ultraviolet light exposure and smoking status. Nonetheless, these results do not support an association between ionizing radiation from repeated head CT scans and cataract formation.

The Great Lakes provide habitat to over 160 species of freshwater fish, many of which are ecologically and economically important. Concern for management and conservation of declining fish populations makes it important that accurate identification techniques are used for environmental monitoring programs. DNA barcoding may be an effective alternative to morphological identification for industrial monitoring programs of larval and embryonic fish, but comparisons of the two approaches with species from the Great Lakes are limited. It may be particularly important to examine this issue in the Great Lakes because a relatively young group of post-glacial fish species are present which may be difficult to resolve using morphology or genetics. Six hundred and fifty seven larval fish were identified from Lake Huron (Ontario, Canada), using morphology and DNA barcoding. DNA barcoding was used to identify 103 embryos that morphology could not identify. Morphological identification and DNA barcoding had a percent similarity of 76.9%, 96.6% and 96.6% at the species, genus, and family levels, respectively. Thirty-seven specimens were damaged and unidentifiable using morphology; 35 of these were successfully identified using DNA barcoding. However, 23 other specimens produced no PCR product for barcoding using 2 different primer sets. Discrepancies between morphology and DNA barcoding were driven by two major factors: inability of cytochrome oxidase I to resolve members of the genus Coregonus and limited resolution of morphological features for Catostomus. Both methods have pros and cons; however, DNA barcoding is more cost-effective and efficient for industrial monitoring programs.

Purpose: Dose and dose rate are both appropriate for estimating risk from internally deposited radioactive materials. We investigated the role of dose rate on lung cancer induction in Beagle dogs following a single inhalation of strontium-90 (90Sr), cerium-144 (144Ce), yttrium-91 (91Y), or yttrium-90 (90Y). As retention of the radionuclide is dependent on biological clearance and physical half-life a representative quantity to describe this complex changing dose rate is needed. Materials and methods: Data were obtained from Beagle dog experiments from the Inhalation Toxicology Research Institute. The authors selected the dose rate at the effective half-life of each radionuclide (DRef). Results: Dogs exposed to DRef (1–100 Gy/day) died within the first year after exposure from acute lung disease. Dogs exposed at lower DRef (0.1–10 Gy/day) died of lung cancer. As DRef decreased further (

During incubation, round whitefish embryos may experience fluctuating or elevated temperatures from natural (e.g., seasonal temperature changes) and/or anthropogenic sources. Anthropogenic sources like once-through cooling discharges from nuclear power plants can also expose embryos to chemicals (e.g., morpholine) and/or radiation. To examine the effects of these potential stressors on embryogenesis, round whitefish were incubated under fluctuating or constant temperatures, with morpholine or 137 Cs gamma rays. We report the percentage of prehatch and posthatch mortality, developmental rate, hatch dynamics, and morphometrics at 4 development stages. Embryos reared at constant temperatures had delayed developmental stage onset and median hatch, higher mortality at constant 8 °C, and lower mortality at ≤5 °C, compared with embryos reared under seasonal temperature regimes. Embryos incubated with ≥500 mg L-1 morpholine (>200× regulatory limits) had advanced hatch, reduced body size, and increased prehatch (100% at 1000 mg L-1 ) and posthatch (≈95% at 500 mg L-1 ) mortality compared with controls. Relative to controls, embryos irradiated with ≥0.16 mGy/d had larger body mass early in development, and all irradiated embryos had decreased posthatch mortality; the lowest dose was >300× discharge limits. Our study suggests that fluctuating or elevated temperatures and high-dose morpholine can alter development rate, hatch dynamics, and growth, and/or increase mortality compared with embryos reared at constant temperatures of ≤5 °C; conversely, low-dose irradiation had transient developmental effects but may benefit early posthatch survival. Environ Toxicol Chem 2018;37:2593-2608. © 2018 SETAC.

Fluctuating incubation temperatures may have significant effects on fish embryogenesis; yet most laboratory-based studies use constant temperatures. For species that experience large, natural seasonal temperature changes during embryogenesis, such as lake whitefish (Coregonus clupeaformis), seasonal temperature regimes are likely optimal for development. Anthropogenic activities can increase average and/or variability of natural incubation temperatures over large (e.g. through climate change) or smaller (e.g. thermal effluent discharge) geographic scales. To investigate this, we incubated lake whitefish embryos under constant (2, 5, or 8°C) and fluctuating temperature regimes. Fluctuating temperature regimes had a base temperature of 2°C with: 1) seasonal temperature changes that modeled natural declines/inclines; 2) tri-weekly +3°C, 1h temperature spikes; or 3) both seasonal temperature changes and temperature spikes. We compared mortality to hatch, morphometrics, and heart rate at three developmental stages. Mortality rate was similar for embryos incubated at constant 2°C, constant 5°C, or with seasonal temperatures, but was significantly greater at constant 8°C. Embryos incubated constantly at >2°C had reduced body growth and yolk consumption compared to embryos incubated with seasonal temperature changes. When measured at the common base temperature of 2°C, embryos incubated at constant 2°C had lower heart rates than embryos incubated with both seasonal temperature changes and temperature spikes. Our study suggests that incubating lake whitefish embryos with constant temperatures may significantly alter development, growth, and heart rate compared to incubating with seasonal temperature changes, emphasizing the need to include seasonal temperature changes in laboratory-based studies.

Ionizing radiation exposure from medical diagnostic imaging has greatly increased over the last few decades. Approximately 80% of patients who undergo medical imaging are exposed to low-dose ionizing radiation (LDIR). Although there is widespread consensus regarding the harmful effects of high doses of radiation, the biological effects of low-linear energy transfer (LET) LDIR is not well understood. LDIR is known to promote oxidative stress, however, these levels may not be large enough to result in genomic mutations. There is emerging evidence that oxidative stress causes heritable modifications via epigenetic mechanisms (DNA methylation, histone modification, noncoding RNA regulation). These epigenetic modifications result in permanent cellular transformations without altering the underlying DNA nucleotide sequence. This review summarizes the major concepts in the field of epigenetics with a focus on the effects of low-LET LDIR (100 mGy) and oxidative stress on epigenetic gene modification. In this review, we show evidence that suggests that LDIR-induced oxidative stress provides a mechanistic link between LDIR and epigenetic gene regulation. We also discuss the potential implication of LDIR exposure during pregnancy where intrauterine fetal development is highly susceptible to oxidative stress-induced epigenetic programing.

Beneficial protective effects may result from an adaptive respose to low dose radiation exposure. However, such benefits must be accompanied by some form of cost because the responsible biological mechanisms are not normally maintained in an upregulated state. It has been suggested that stimulation of adaptive response mechanisms could be metabolically costly, or that the adaptive response could come at a sacrifice to other physiological processes. We exposed developing lake whitefish embryos to a fractionated regime of gamma radiation (662 keV; 0.3 Gy min-1) to determine whether radiation-stimulated growth was accompanied by a trade-off in metabolic efficiency. Developing embryos were exposed at the eyed stage to different radiation doses delivered in four fractions, ranging from 15 mGy to 8 Gy per fraction, with a 14 day separation between dose fractions. Dry weight and standard length measurements were taken 2-5 weeks after delivery of the final radiation exposure and yolk conversion efficiency was estimated by comparing the unpreserved dry weight of the yolk to the unpreserved yolk-free dry weight of the embryos and normalizing for size-related differences in somatic maintenance. Our results show that the irradiated embryos were 8-10% heavier than the controls but yolk conversion efficiency was slightly improved. This finding demonstrates that stimulated growth in developing lake whitefish embryos is not "paid for" by a trade-off in the efficiency of yolk conversion.

Lake whitefish ( Coregonus clupeaformis ) embryos were exposed to thermal stress (TS) at different developmental stages to determine when the heat shock response (HSR) can be initiated and if it is altered by exposure to repeated TS. First, embryos were subject to one of three different TS temperatures (6, 9, or 12 °C above control) at 4 points in development (21, 38, 60 and 70 days post-fertilisation (dpf)) for 2 h followed by a 2 h recovery to understand the ontogeny of the HSR. A second experiment explored the effects of repeated TS on the HSR in embryos from 15 to 75 dpf. Embryos were subjected to one of two TS regimes; +6 °C TS for 1 h every 6 days or +9 °C TS for 1 h every 6 days. Following a 2 h recovery, a subset of embryos was sampled. Our results show that embryos could initiate a HSR via upregulation of heat shock protein 70 ( hsp70 ) mRNA at all developmental ages studied, but that this response varied with age and was only observed with a TS of +9 or +12 °C. In comparison, when embryos received multiple TS treatments, hsp70 was not induced in response to the 1 h TS and 2 h recovery, and a downregulation was observed at 39 dpf. Downregulation of hsp47 and hsp90α mRNA was also observed in early age embryos. Collectively, these data suggest that embryos are capable of initiating a HSR at early age and throughout embryogenesis, but that repeated TS can alter the HSR, and may result in either reduced responsiveness or a downregulation of inducible hsps . Our findings warrant further investigation into both the short- and long-term effects of repeated TS on lake whitefish development.

Cellular transformation assays have been utilized for many years as powerful in vitro methods for examining neoplastic transformation potential/frequency and mechanisms of carcinogenesis for both chemical and radiological carcinogens. These mouse and human cell based assays are labor intensive but do provide quantitative information on the numbers of neoplastically transformed foci produced after carcinogenic exposure and potential molecular mechanisms involved. Several mouse and human cell systems have been generated to undertake these studies, and they vary in experimental length and endpoint assessment. The CGL1 human cell hybrid neoplastic model is a non-tumorigenic pre-neoplastic cell that was derived from the fusion of HeLa cervical cancer cells and a normal human skin fibroblast. It has been utilized for the several decades to study the carcinogenic/neoplastic transformation potential of a variety of ionizing radiation doses, dose rates and radiation types, including UV, X ray, gamma ray, neutrons, protons and alpha particles. It is unique in that the CGL1 assay has a relatively short assay time of 18-21 days, and rather than relying on morphological endpoints to detect neoplastic transformation utilizes a simple staining method that detects the tumorigenic marker alkaline phosphatase on the neoplastically transformed cells cell surface. In addition to being of human origin, the CGL1 assay is able to detect and quantify the carcinogenic potential of very low doses of ionizing radiation (in the mGy range), and utilizes a neoplastic endpoint (re-expression of alkaline phosphatase) that can be detected on both viable and paraformaldehyde fixed cells. In this article, we review the history of the CGL1 neoplastic transformation model system from its initial development through the wide variety of studies examining the effects of all types of ionizing radiation on neoplastic transformation. In addition, we discuss the potential of the CGL1 model system to investigate the effects of near zero background radiation levels available within the radiation biology lab we have established in SNOLAB.

Computed tomography (CT) scans are a routine diagnostic imaging technique that utilize low-energy X rays with an average absorbed dose of approximately 10 mGy per clinical whole-body CT scan. The growing use of CT scans in the clinic has raised concern of increased carcinogenic risk in patients exposed to ionizing radiation from diagnostic procedures. The goal of this study was to better understand cancer risk associated with low-dose exposures from CT scans. Historically, low-dose exposure preceding a larger challenge dose increases tumor latency, but does little to impact tumor frequency in Trp53+/– mice. To assess the effects of CT scans specifically on tumor progression, whole-body CT scans (10 mGy/scan, 75 kVp) were started at four weeks after 4 Gy irradiation, to allow for completion of tumor initiation. The mice were exposed to weekly CT scans for ten consecutive weeks. In this study, we show that CT scans modify cellular end points commonly associated with carcinogenesis in cancer-prone Trp53+/– h...

Reliable human data on the effects of prenatal exposure to ionizing radiation are largely based on high-dose exposures. Exposure to low doses may produce effects that are not easily observable at birth, and may persist over the course of the offspring's postnatal life. This is important when considering fetal programing, a phenomenon characterized by changes in offspring phenotype due to a stress experienced in utero. In this review, we briefly summarize the known effects of both high- and low-dose exposure to ionizing radiation during pregnancy in humans. There is a major consensus that the atomic bomb survivors' data shows increased incidence of microcephaly and reductions in IQ of A-bomb survivors, whereas, with diagnostic radiography in utero there is no conclusive evidence of increased cancer risk. Due to the relatively limited data (particularly for low-dose exposures) in humans, animal models have emerged as an important tool to study prenatal effects of radiation. These animal models enable researchers to manipulate various experimental parameters and make it possible to analyze a wider variety of end points. In this review, we discuss the major findings from studies using mouse and rat models to examine prenatal ionizing radiation effects in postnatal development of the offspring. In addition, we broadly categorize trends across studies within three major stages of development: pre-implantation, organogenesis and fetal development. Overall, long-term effects of prenatal radiation exposure (including the possible role on the developmental programing of disease) are important factors to consider when assessing radiation risk, since these effects are of relevance even in the low-dose range.

A laboratory flume was constructed to examine substrate effects on aquatic development. The flume was designed as a once-through system with a submerged cobble-filled corebox. Lake whitefish (Coregonus clupeaformis) embryos and temperature probes were deployed at multiple sites within the cobble and in the open water channel. Embryos were incubated in the flume for two different experimental periods: one to examine substrate impacts during natural lake cooling (37 days: 5 December 2016 to 10 January 2017) and the second to investigate substrate effects while administering a twice weekly 1 h heat shock (51 days: 11 January to 2 March 2017). During incubation, no significant difference was found in the average temperature between locations; however, temperatures were more stable within the cobble. Following both incubation periods, embryos retrieved from the cobble were significantly smaller in both dry mass and body length by up to 20%. These results demonstrate differences between embryos submerged in a cobble substrate and in the open water column, highlighting the need to consider the physical influences from the incubation environment when assessing development effects as part of any scientific study or environmental assessment.

Purpose: Developmental programming involves an adverse intrauterine environment which can result in offspring phenotype changes following birth. The developmental programming of hypertension has been reported to possibly involve oxidative stress at the cellular level. Ionizing radiation produces oxidative stress, even at low doses, and irradiation of animals is often coupled with potential sources of maternal stress such as transportation of animals or repeated handling. Materials and methods: Pregnant C57Bl/6J mice were irradiated on gestational day 15 with 5-1000 mGy 137Cs gamma radiation. Post-natal weight, blood pressure (BP) and heart rate (HR) were measured. Radiation had minimal effects at doses ≤300 mGy, but 1000 mGy caused a significant reduction in HR in male pups and growth reduction at 16 weeks of age in both genders. The sham-irradiation protocol included repeated transportation in order to acclimate animals to transport. However, it may have resulted in programming, as sham-irradiation alone resulted in elevated BP measures compared to the offspring of animals that were never transported. Results and conclusions: Overall, there were minimal effects on cardiovascular measures or offspring weight due to irradiation except at 1000 mGy. The presence of maternal stress, a known trigger of developmental programming, may have confounded any potential irradiation effects.

Extensive research has been conducted investigating the effects of ionizing radiation on biological systems, including specific focus at low doses. However, at the surface of the planet, there is the ubiquitous presence of ionizing natural background radiation (NBR) from sources both terrestrial and cosmic. We are currently conducting radiobiological experiments examining the impacts of sub-NBR exposure within SNOLAB. SNOLAB is a deep underground research laboratory in Sudbury, Ontario, Canada located 2 km beneath the surface of the planet. At this depth, significant shielding of NBR components is provided by the rock overburden. Here, we describe a Specialized Tissue Culture Incubator (STCI) that was engineered to significantly reduce background ionizing radiation levels. The STCI was installed 2 km deep underground within SNOLAB. It was designed to allow precise control of experimental variables such as temperature, atmospheric gas composition and humidity. More importantly, the STCI was designed to reduce radiological contaminants present within the underground laboratory. Quantitative measurements validated the STCI is capable of maintaining an appropriate experimental environment for sub-NBR experiments. This included reduction of sub-surface radiological contaminants, most notably radon gas. The STCI presents a truly novel piece of infrastructure enabling future research into the effects of sub-NBR exposure in a highly unique laboratory setting.

Chemicals used in the prevention of corrosion and biofouling may be released into the environment via industrial cooling water discharges. We assessed the impacts of two commonly used chemicals, morpholine and sodium hypochlorite, on development in lake whitefish (Coregonus clupeaformis). Embryos were exposed chronically, beginning at fertilization or at the eyed stage. Acute 96 hour exposures were also examined at four development stages. Chronic morpholine resulted in an LC50 of 219 ± 54 mg/L when exposure began at fertilization and 674 ± 12 mg/L when exposure began at the eyed stage, suggesting that embryos are more sensitive earlier in development. Chronic morpholine exposure advanced hatching by up to 30% and the early hatching embryos were up to 10% smaller in body length. A decrease in yolk conversion efficiency was also observed in embryos exposed to chronic morpholine concentrations of 1000 mg/L. The majority of effects from morpholine exposure manifested near hatch, possibly reflecting changes in chorion permeability at the end of embryonic development. Sodium hypochlorite only impacted survival with chronic exposure from fertilization, where the total residual chlorine LC50 was 0.52 ± 0.11 mg/L. Acute exposures to both chemicals had minimal effects up to the highest tested concentrations. Overall, these results suggest that the risk during development from exposure to morpholine and sodium hypochlorite is low under normal operating conditions. This article is protected by copyright. All rights reserved

Lake Whitefish Coregonus clupeaformis is the most commercially valuable species in Lake Huron. The fishery for this species has historically been managed based on 25 management units (17 in Canada, 8 in the USA). However, congruence between the contemporary population structure of Lake Whitefish and management units is poorly understood. We used stable isotopes of carbon (δ13C) and nitrogen (δ15N), food web markers that reflect patterns in resource use (i.e., prey, location, habitat), to assess the population structure of spawning-phase Lake Whitefish collected from 32 sites (1,474 fish) across Lake Huron. We found large isotopic variation among fish from different sites (ranges: δ13C = 10.2‰, δ15N = 5.5‰) and variable niche size and levels of overlap (standard ellipse area = 1.0–4.3‰2). Lake Huron contained spawning-phase fish from four major isotopic clusters largely defined by extensive variation in δ13C, and the isotopic composition of fish sampled was spatially structured both within and betw...

Lipids serve as energy sources, structural components, and signaling molecules during fish embryonic development, and utilization of lipids may vary with temperature. Embryonic energy utilization under different temperatures is an important area of research in light of the changing global climate. Therefore, we examined percent lipid content and fatty acid profiles of lake whitefish ( Coregonus clupeaformis ) throughout embryonic development at three incubation temperatures. We sampled fertilized eggs and embryos at gastrulation, eyed and fin flutter stages following chronic incubation at temperatures of 1.8, 4.9 and 8.0 °C. Hatchlings were also sampled following incubation at temperatures of 3.3, 4.9 and 8.0 °C. Fertilized eggs had an initial high percentage of dry mass composed of lipid (percent lipid content; ~ 29%) consisting of ~ 20% saturated fatty acids (SFA), ~ 32% monounsaturated fatty acids (MUFA), ~ 44% polyunsaturated fatty acids (PUFA), and 4% unidentified. The most abundant fatty acids were 16:0, 16:1, 18:1(n-9c), 20:4(n-6), 20:5(n-3) and 22:6(n-3). This lipid profile matches that of other cold-water fish species. Percent lipid content increased during embryonic development, suggesting protein or other yolk components were preferentially used for energy. Total percentage of MUFA decreased during development, which indicated MUFA were the primary lipid catabolized for energy during embryonic development. Total percentage of PUFA increased during development, driven largely by an increase in 22:6(n-3). Temperature did not influence percent lipid content or percent MUFA at any development stage, and had inconsistent effects on percent SFA and percent PUFA during development. Thus, lake whitefish embryos appear to be highly adapted to low temperatures, and do not alter lipids in response to temperature within their natural incubation conditions.

Thermal discharges released from industrial cooling water systems represent a potential environmental risk to fish species that spawn in nearshore waters. We investigated the impacts of in situ incubation of lake whitefish (Coregonus clupeaformis) embryos in the vicinity of a nuclear generating station. Over 3 consecutive years, fertilized embryos were deployed in Lake Huron using custom-built incubation chambers coupled with data loggers to monitor water temperature. Temperatures at sites in the vicinity of the thermal discharge were significantly elevated compared with reference locations, with mean winter temperatures up to 3 °C warmer. Temperatures were also more variable at these sites, with a significantly greater daily temperature range and rate of change. Embryos developing at discharge sites were significantly larger with smaller yolks than those from the reference stations, suggesting an advanced growth. This increased growth was supported by thermal data, with discharge sites predicted to be more than 10% advanced based on growth rate modelling. These temperature changes and increase in development rate are below thresholds for embryonic mortality but could potentially impact posthatch larval survival.