Protracted Exposure to a Sub-background Radiation Environment Negatively Impacts the Anhydrobiotic Recovery of Desiccated Yeast Sentinels.

ABSTRACT: Experiments that examine the impacts of subnatural background radiation exposure provide a unique approach to studying the biological effects of low-dose radiation. These experiments often need to be conducted in deep underground laboratories in order to filter surface-level cosmic radiation. This presents some logistical challenges in experimental design and necessitates a model organism with minimal maintenance. As such, desiccated yeast ( Saccharomyces cerevisiae ) is an ideal model system for these investigations. This study aimed to determine the impact of prolonged sub-background radiation exposure in anhydrobiotic (desiccated) yeast at SNOLAB in Sudbury, Ontario, Canada. Two yeast strains were used: a normal wild type and an isogenic recombinational repair-deficient rad51 knockout strain ( rad51 Δ). Desiccated yeast samples were stored in the normal background surface control laboratory (68.0 nGy h -1 ) and in the sub-background environment within SNOLAB (10.1 nGy h -1 ) for up to 48 wk. Post-rehydration survival, growth rate, and metabolic activity were assessed at multiple time points. Survival in the sub-background environment was significantly reduced by a factor of 1.39 and 2.67 in the wild type and rad51 ∆ strains, respectively. Post-rehydration metabolic activity measured via alamarBlue reduction remained unchanged in the wild type strain but was 26% lower in the sub-background rad51 ∆ strain. These results demonstrate that removing natural background radiation negatively impacts the survival and metabolism of desiccated yeast, highlighting the potential importance of natural radiation exposure in maintaining homeostasis of living organisms.

Assessment of Cataract Risk after Diagnostic Head CT Scan Radiation Exposure in Ontario, Canada.

Ionizing radiation is one of the known risk factors for cataract development, however, there is still debate regarding the level of risk after low dose exposures. One of the largest sources of radiation exposure to the lens of the eye is diagnostic CT scans. The aim of this study was to examine whether ionizing radiation associated with head CT scans increases cataract risk in residents of Ontario, Canada. Data were collected from January 1, 1994 to December 31, 2015 (22 years) from anonymized Ontario Health Insurance Plan (OHIP) medical records for over 16 million subjects. A lens dose was estimated for each CT scan using the National Cancer Institute dosimetry system for CT (NCICT) program combined with Canada-specific CTDIvol data. Multivariate Cox proportional hazards analysis was performed with cataract extraction surgery as the primary outcome and lens dose as the main variable of interest, with inclusion of various medical and demographic covariates. Lag periods of 3, 5 and 7 years were incorporated. When lens dose was treated as a continuous variable, hazard ratios (per 100 mGy) ranged from 0.82 (0.80-0.84) to 1.10 (1.09-1.11) depending on the lag period. As a secondary analysis, when individuals were binned based on their total cumulative dose, no significant dose response pattern was observed in the low dose region. Overall, within the bounds of this study, the data do not support an increased risk of vision impairing cataracts after diagnostic head CT scan radiation exposure.

Overexpression of FRA1 (FOSL1) Leads to Global Transcriptional Perturbations, Reduced Cellular Adhesion and Altered Cell Cycle Progression.

FRA1 (FOSL1) is a transcription factor and a member of the activator protein-1 superfamily. FRA1 is expressed in most tissues at low levels, and its expression is robustly induced in response to extracellular signals, leading to downstream cellular processes. However, abnormal FRA1 overexpression has been reported in various pathological states, including tumor progression and inflammation. To date, the molecular effects of FRA1 overexpression are still not understood. Therefore, the aim of this study was to investigate the transcriptional and functional effects of FRA1 overexpression using the CGL1 human hybrid cell line. FRA1-overexpressing CGL1 cells were generated using stably integrated CRISPR-mediated transcriptional activation, resulting in a 2-3 fold increase in FRA1 mRNA and protein levels. RNA-sequencing identified 298 differentially expressed genes with FRA1 overexpression. Gene ontology analysis showed numerous molecular networks enriched with FRA1 overexpression, including transcription-factor binding, regulation of the extracellular matrix and adhesion, and a variety of signaling processes, including protein kinase activity and chemokine signaling. In addition, cell functional assays demonstrated reduced cell adherence to fibronectin and collagen with FRA1 overexpression and altered cell cycle progression. Taken together, this study unravels the transcriptional response mediated by FRA1 overexpression and establishes the role of FRA1 in adhesion and cell cycle progression.

Effect of elevated embryonic incubation temperature on the temperature preference of juvenile lake (Coregonus clupeaformis) and round whitefish (Prosopium cylindraceum).

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 months (Lake whitefish only) and 12 months of age (both species) using a shuttle box system. Round whitefish preferred a cooler temperature when incubated at 2 and 6°C compared with 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.

Genomic Loss and Epigenetic Silencing of the FOSL1 Tumor Suppressor Gene in Radiation-induced Neoplastic Transformation of Human CGL1 Cells Alters the Tumorigenic Phenotype In Vitro and In Vivo.

The CGL1 human hybrid cell system has been utilized for many decades as an excellent cellular tool for investigating neoplastic transformation. Substantial work has been done previously implicating genetic factors related to chromosome 11 to the alteration of tumorigenic phenotype in CGL1 cells. This includes candidate tumor suppressor gene FOSL1, a member of the AP-1 transcription factor complex which encodes for protein FRA1. Here we present novel evidence supporting the role of FOSL1 in the suppression of tumorigenicity in segregants of the CGL1 system. Gamma-induced mutant (GIM) and control (CON) cells were isolated from 7 Gy gamma-irradiated CGL1s. Western, Southern and Northern blot analysis were utilized to assess FOSL1/FRA1 expression as well as methylation studies. GIMs were transfected to re-express FRA1 and in vivo tumorigenicity studies were conducted. Global transcriptomic microarray and RT-qPCR analysis were used to further characterize these unique cell segregants. GIMs were found to be tumorigenic in vivo when injected into nude mice whereas CON cells were not. GIMs show loss of Fosl/FRA1 expression as confirmed by Western blot. Southern and Northern blot analysis further reveals that FRA1 reduction in tumorigenic CGL1 segregants is likely due to transcriptional suppression. Results suggest that radiation-induced neoplastic transformation of CGL1 is in part due to silencing of the FOSL1 tumor suppressor gene promoter by methylation. The radiation-induced tumorigenic GIMs transfected to re-express FRA1 resulted in suppression of subcutaneous tumor growth in nude mice in vivo. Global microarray analysis and RT-qPCR validation elucidated several hundred differentially expressed genes. Downstream analysis reveals a significant number of altered pathways and enriched Gene Ontology terms genes related to cellular adhesion, proliferation, and migration. Together these findings provide strong evidence that FRA1 is a tumor suppressor gene deleted and epigenetically silenced after ionizing radiation-induced neoplastic transformation in the CGL1 human hybrid cell system.

The REPAIR Project, a Deep-Underground Radiobiology Experiment Investigating the Biological Effects of Natural Background Radiation: The First 6 Years.

In 2017, a special edition of Radiation Research was published [Oct; Vol. 188 4.2 (https://bioone.org/journals/radiation-research/volume-188/issue-4.2)] which focused on a recently established radiobiology project within SNOLAB, a unique deep-underground research facility. This special edition included original articles, reviews and commentaries relevant to the research goals of this new project which was titled Researching the Effects of the Presence and Absence of Ionizing Radiation (REPAIR). These research goals were founded in understanding the biological effects of terrestrial and cosmic natural background radiation (NBR). Since 2017, REPAIR has evolved into a sub-NBR radiobiology research program which investigates these effects using multiple model systems and various biological endpoints. This paper summarizes the evolution of the REPAIR project over the first 6-years including its experimental scope and capabilities as well as research accomplishments.

Low-Dose Hemibody Radiation, a Treatment Option for Recurrent Prostate Cancer: A Phase 2 Single-Arm Trial.

Purpose: 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%. Methods and Materials: 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. Results: 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 × 109/L, leukocyte ≤3 × 109/L, granulocyte ≤2 × 109/L). Conclusions: Our 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.

Identification of Radiation-Induced miRNA Biomarkers Using the CGL1 Cell Model System.

MicroRNAs (miRNAs) have emerged as a potential class of biomolecules for diagnostic biomarker applications. miRNAs are small non-coding RNA molecules, produced and released by cells in response to various stimuli, that demonstrate remarkable stability in a wide range of biological fluids, in extreme pH fluctuations, and after multiple freeze-thaw cycles. Given these advantages, identification of miRNA-based biomarkers for radiation exposures can contribute to the development of reliable biological dosimetry methods, especially for low-dose radiation (LDR) exposures. In this study, an miRNAome next-generation sequencing (NGS) approach was utilized to identify novel radiation-induced miRNA gene changes within the CGL1 human cell line. Here, irradiations of 10, 100, and 1000 mGy were performed and the samples were collected 1, 6, and 24 h post-irradiation. Corroboration of the miRNAome results with RT-qPCR verification confirmed the identification of numerous radiation-induced miRNA expression changes at all doses assessed. Further evaluation of select radiation-induced miRNAs, including miR-1228-3p and miR-758-5p, as well as their downstream mRNA targets, Ube2d2, Ppp2r2d, and Id2, demonstrated significantly dysregulated reciprocal expression patterns. Further evaluation is needed to determine whether the candidate miRNA biomarkers identified in this study can serve as suitable targets for radiation biodosimetry applications.

Thermal acclimation alters both basal heat shock protein gene expression and the heat shock response in juvenile lake whitefish (Coregonus clupeaformis).

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 hsp90ß 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.

The heat shock response shows plasticity in embryonic lake whitefish (Coregonus clupeaformis) exposed to repeated thermal stress.

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 °C 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.

Space Radiation Protection Countermeasures in Microgravity and Planetary Exploration.

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.

DOSIMETRIC CHARACTERISATION OF A SUB-NATURAL BACKGROUND RADIATION ENVIRONMENT FOR RADIOBIOLOGY INVESTIGATIONS.

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.

Lasting Effects of Low to Non-Lethal Radiation Exposure during Late Gestation on Offspring's Cardiac Metabolism and Oxidative Stress.

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.

Relative Biological Effectiveness and Non-Poissonian Distribution of Dicentric Chromosome Aberrations following Californium-252 Neutron Exposures of Human Peripheral Blood Lymphocytes.

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.

Unchanged cardiovascular and respiratory outcomes in healthy C57Bl/6 mice after in utero exposure to ionizing radiation.

BACKGROUND: 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. MATERIALS AND METHODS: Pregnant C57Bl/6 mice were whole-body irradiated at gestational day 15 with a 137Cs gamma radiation emitting source at 0 mGy (sham), 50 mGy, 300 mGy, or 1000 mGy. Post weaning weight and blood pressure measurements were taken weekly for both male and female pups until euthanasia at 16-17 weeks postnatal age. Immediately following, the trachea was cannulated, and the lungs and heart excised. The lung was then examined to assess respiratory physiological outcomes. RESULTS AND CONCLUSIONS: In utero exposures to 1000 mGy caused significant growth reduction compared to sham irradiated, which remained persistent for both male and female pups. Growth restriction was not observed for lower exposures. There was no significant change in any cardiovascular or respiratory outcomes measured. Overall, intrauterine exposures to ionizing radiation does not appear to significantly alter the development of the cardiovascular and respiratory system in C57Bl/6 pups up to 17 weeks postnatal age.

A novel specialized tissue culture incubator designed and engineered for radiobiology experiments in a sub-natural background radiation research environment.

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.

Relative Biological Effectiveness and Non-Poissonian Distribution of Dicentric Chromosome Aberrations after Californium-252 Neutron Exposures of Human Peripheral Blood Lymphocytes.

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 formation was 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 enough lymphocyte nuclei are scored, chromosome aberration clustering can be observed.

A radon chamber specifically designed for environmentally relevant exposures of small animals.

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.

Dose threshold for radiation induced fetal programming in a mouse model at 4 months of age: Hepatic expression of genes and proteins involved in glucose metabolism and glucose uptake in brown adipose tissue.

Exposure to ionizing radiation contributing to negative health outcomes is a widespread concern. However, the impact of low dose and sub-lethal dose radiation (SLDR) exposures remain contentious, particularly in pregnant women who represent a vulnerable group. The fetal programming hypothesis states that an adverse in utero environment or stress during development of an embryo or fetus can result in permanent physiologic changes often resulting in progressive metabolic dysfunction with age. To assess changes in gene expression profiles of glucose/insulin signaling and lipid metabolism caused by radiation exposure in utero, pregnant C57Bl/6J mice were irradiated using a dose response ranging from low dose to SLDR and compared to a Sham-irradiated group. mRNA expression analysis in 16 week old offspring (n = 84) revealed that genes involved in metabolic function including glucose metabolism, insulin signaling and lipid metabolism were unaffected by prenatal radiation exposures up to 300 mGy. However, female offspring of dams exposed to 1000 mGy had upregulated expression of genes contributing to insulin resistance and gluconeogenesis. In a second cohort of mice, the effects of SLDR on fetal programming of hepatic SOCS3 and PEPCK protein expression were assessed. 4 month old female offspring of dams irradiated at 1000 mGy had: 1) increased liver weights, 2) increased hepatic expression of proteins involved in glucose metabolism and 3) increased 18F-fluorodeoxyglucose (FDG) uptake in interscapular brown adipose tissue (IBAT) measured by positron emission tomography (PET) (n = 25). The results of this study indicate that prenatal radiation exposure does not affect metabolic function up to 300 mGy and 1000 mGy may be a threshold dose for sex-specific alterations in glucose uptake and hepatic gene and protein expression of SOCS3, PEPCK, PPARGC1A and PPARGC1B. These findings suggest that SLDR doses alter glucose uptake in IBAT and hepatic gene and protein expression of offspring and these changes may progress with age.

Modifying effects of a cobble substrate on thermal environments and implications for embryonic development in lake whitefish (Coregonus clupeaformis).

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.