Publications by authors named "Steve Wiseman"

92 Publications

The brominated flame retardant, TBCO, impairs oocyte maturation in zebrafish (Danio rerio).

Aquat Toxicol 2021 Aug 3;238:105929. Epub 2021 Aug 3.

Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, T1K 3M4, Canada; Intersectoral Centre for Endocrine Disruptor Analysis (ICEDA), Institut National de la Recherche Scientifique (INRS), Centre Eau Terre Environnement, Québec City, QC, G1K 9A9, Canada; Water Institute for Sustainable Environments, University of Lethbridge, Lethbridge, AB, T1K 3M4, Canada. Electronic address:

The brominated flame retardant, 1,2,5,6-tetrabromocyclooctane (TBCO), has been shown to decrease fecundity in Japanese medaka (Oryzias latipes) and there is indirect evidence from analysis of the transcriptome and proteome that this effect might be due to impaired oogenesis. An assay for disruption of oocyte maturation by chemical stressors has not been developed in Japanese medaka. Thus, using zebrafish (Danio rerio) as a model, objectives of the present study were to determine whether exposure to TBCO has effects on maturation of oocytes and to investigate potential mechanisms. Sexually mature female zebrafish were given a diet of 35.3 or 628.8 μg TBCO / g food for 14 days after which, stage IV oocytes were isolated to assess maturation in response to maturation inducing hormone. To explore potential molecular mechanisms, abundances of mRNAs of a suite of genes that regulate oocyte maturation were quantified by use of quantitative real-time PCR, and abundances of microRNAs were determined by use of miRNAseq. Ex vivo maturation of oocytes from fish exposed to TBCO was significantly less than maturation of oocytes from control fish. The percentage of oocytes which matured from control fish and those exposed to low and high TBCO were 89, 71, and 67%, respectively. Among the suite of genes known to regulate oocyte maturation, mRNA abundance of insulin like growth factor-3 was decreased by 1.64- and 3.44-fold in stage IV oocytes from females given the low and high concentrations of TBCO, respectively, compared to the control group. Abundances of microRNAs regulating the expression of proteins that regulate oocyte maturation, including processes related to insulin-like growth factor, were significantly different in stage IV oocytes from fish exposed to TBCO. Overall, results of this study indicated that impaired oocyte maturation might be a mechanism of reduced reproductive performance in TBCO-exposed fish. Results also suggested that effects of TBCO on oocyte maturation might be due to molecular perturbations on insulin-like growth factor signaling and expression of microRNAs.
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http://dx.doi.org/10.1016/j.aquatox.2021.105929DOI Listing
August 2021

Mechanism of copper nanoparticle toxicity in rainbow trout olfactory mucosa.

Environ Pollut 2021 Sep 16;284:117141. Epub 2021 Apr 16.

Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, Canada.

Chemosensory perception is crucial for fish reproduction and survival. Direct contact of olfactory neuroepithelium to the surrounding environment makes it vulnerable to contaminants in aquatic ecosystems. Copper nanoparticles (CuNPs), which are increasingly used in commercial and domestic applications due their exceptional properties, can impair fish olfactory function. However, the molecular events underlying olfactory toxicity of CuNPs are largely unexplored. Our results suggested that CuNPs were bioavailable to olfactory mucosal cells. Using RNA-seq, we compared the effect of CuNPs and copper ions (Cu) on gene transcript profiles of rainbow trout (Oncorhynchus mykiss) olfactory mucosa. The narrow overlap in differential gene expression between the CuNP- and Cu-exposed fish revealed that these two contaminants exert their effects through distinct mechanisms. We propose a transcript-based conceptual model that shows that olfactory signal transduction, calcium homeostasis, and synaptic vesicular signaling were affected by CuNPs in the olfactory sensory neurons (OSNs). Neuroregenerative pathways were also impaired by CuNPs. In contrast, Cu did not induce toxicity pathways and rather upregulated regeneration pathways. Both Cu treatments reduced immune system pathway transcripts. However, suppression of transcripts that were associated with inflammatory signaling was only observed with CuNPs. Neither oxidative stress nor apoptosis were triggered by Cu or CuNPs in mucosal cells. Dysregulation of transcripts that regulate function, maintenance, and reestablishment of damaged olfactory mucosa represents critical mechanisms of toxicity of CuNPs. The loss of olfaction by CuNPs may impact survival of rainbow trout and impose an ecological risk to fish populations in contaminated environments.
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http://dx.doi.org/10.1016/j.envpol.2021.117141DOI Listing
September 2021

H NMR based metabolomic profiling of early life stage zebrafish (Danio rerio) exposed to a water-soluble fraction of weathered sediment-bound diluted bitumen.

Aquat Toxicol 2021 Jan 29;232:105766. Epub 2021 Jan 29.

Department of Biological Sciences, University of Lethbridge, Lethbridge, AB, T1K 3M4, Canada; Water Institute for Sustainable Environments, University of Lethbridge, Lethbridge, AB, T1K 3M4, Canada. Electronic address:

Spills of diluted bitumen (dilbit) from pipelines pose a risk to the health of aquatic organisms, including fish, and with expected increases in production and transportation of dilbit, these risks could increase. To date, the majority of studies have investigated effects of fresh dilbit on aquatic organisms, but little is known about effects of weathered sediment-bound dilbit, including mechanisms of toxicity. The goal of this study was to use H NMR based metabolomics to identify altered metabolites and pathways in early life-stages of zebrafish (Danio rerio) exposed to a sediment derived water-soluble fraction of dilbit (SDWSF) to better understand mechanisms of adverse effects. Zebrafish embryos exposed to the SDWSF until 120 h post-fertilization exhibited increased prevalence of pericardial edema, yolk sac edema, and swim bladder malformations that are typical of exposure to fresh dilbit. Concentrations of nine metabolites (alanine, glutamine, lysine, threonine, tyrosine, betaine, taurine, inosine, and glycerol) were significantly altered in embryos exposed to SDWSF. Pathway topology analysis revealed four potentially impacted pathways: 1) phenylalanine, tyrosine, and tryptophan biosynthesis, 2) taurine and hypotaurine metabolism, 3) alanine, aspartate, and glutamate metabolism, and 4) glycine, serine, and threonine metabolism. Altered metabolites were linked to several biological process, that when perturbed could be key events in mechanisms of developmental effects observed in embryos. Future studies should further investigate the role of perturbations to these metabolites and pathways to determine the specific role they might play in adverse effects of exposure to dilbit.
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http://dx.doi.org/10.1016/j.aquatox.2021.105766DOI Listing
January 2021

Toxicity of Weathered Sediment-Bound Dilbit to Early Life Stages of Zebrafish ().

Environ Sci Technol 2021 02 15;55(3):1721-1729. Epub 2021 Jan 15.

Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta T1K 3M4, Canada.

Due to high viscosity, bitumen extracted from the Alberta oil sands is diluted with natural gas condensates to form diluted bitumen (dilbit) to facilitate transport through pipelines. Dilbit that is spilled into or near a waterbody is subject to environmental weathering processes such as evaporation and interaction with sediments. This is the first study that assessed the toxicity of weathered sediment-bound dilbit (WSD) to fish early life stages. Exposure of zebrafish () embryos to water-soluble fractions (WSFs) or water-accommodated fractions (WAFs) of WSD from 30 min to 120 h postfertilization resulted in pericardial edema, yolk sac edema, and incidences of uninflated swim bladder. The presence of oil-mineral aggregates (OMAs) in the WAFs greatly increased toxicity, despite all fractions having similar concentrations of dissolved polycyclic aromatic hydrocarbons (PAHs). There were greater mRNA abundances in larvae exposed to WAFs, suggesting that there were differences in bioavailability of PAHs between fractions. However, there was little evidence that embryotoxicity was caused by oxidative stress. Results suggest that evaporation and sediment interaction do not completely attenuate toxicity of dilbit to zebrafish early life stages, and OMAs in exposures exacerbate toxicity.
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http://dx.doi.org/10.1021/acs.est.0c06349DOI Listing
February 2021

Identification of molecular toxicity pathways across early life-stages of zebrafish exposed to PCB126 using a whole transcriptomics approach.

Ecotoxicol Environ Saf 2021 Jan 11;208:111716. Epub 2020 Dec 11.

Institute for Environmental Research, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany; Department of Evolutionary Ecology and Environmental Toxicology, Goethe University Frankfurt, Max-von-Laue-Str. 13, 60438 Frankfurt am Main, Germany.

Although withdrawn from the market in the 1980s, polychlorinated biphenyls (PCBs) are still found ubiquitously in the aquatic environment and pose a serious risk to biota due to their teratogenic potential. In fish, early life-stages are often considered most sensitive with regard to their exposure to PCBs and other dioxin-like compounds. However, little is known about the molecular drivers of the frequently observed teratogenic effects. Therefore, the aims of our study were to: (1) characterize the baseline transcriptome profiles at different embryonic life-stages in zebrafish (Danio rerio); and (2) to identify the molecular response to PCB exposure and life-stage specific-effects of the chemical on associated processes. For both objectives, embryos were sampled at 12, 48, and 96 h post-fertilization (hpf) and subjected to Illumina sequence-by-synthesis and RNAseq analysis. Results revealed that with increasing age more genes and related pathways were upregulated both in terms of number and magnitude. Yet, other transcripts followed an opposite pattern with greater transcript abundance at the earlier time points. Additionally, embryos were exposed to PCB126, a potent agonist of the aryl hydrocarbon receptor (AHR). ClueGO network analysis revealed significant enrichment of genes associated with basic cell metabolism, communication, and homeostasis as well as eye development, muscle formation, and skeletal formation. We selected eight genes involved in the affected pathways for an in-depth characterization of their regulation throughout normal embryogenesis and after exposure to PCB126 by quantification of transcript abundances every 12 h until 118 hpf. Among these, fgf7 and c9 stood out because of their strong upregulation by PCB126 exposure at 48 and 96 hpf, respectively. Cyp2aa12 was upregulated from 84 hpf on. Fabp10ab, myhz1.1, col8a1a, sulf1, and opn1sw1 displayed specific regulation depending on the developmental stage. Overall, we demonstrate that (1) the developmental transcriptome of zebrafish is highly dynamic, and (2) dysregulation of gene expression by exposure to PCB126 was significant and in several cases not directly connected to AHR-signaling. Hence, this study improves the understanding of linkages between molecular events and apical outcomes that are of regulatory relevance.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111716DOI Listing
January 2021

Effects of the brominated flame retardant, TBCO, on development of zebrafish (Danio rerio) embryos.

Chemosphere 2021 Mar 4;266:129195. Epub 2020 Dec 4.

Department of Biological Sciences, University of Lethbridge, Lethbridge, AB, T1K 3M4, Canada; Water Institute for Sustainable Environments (WISE), University of Lethbridge, Lethbridge, AB, T1K 3M4, Canada. Electronic address:

Brominated flame retardants (BFRs) can enter aquatic environments where they can have adverse effects on organisms. The BFR, 1,2,5,6-Tetrabromocyclooctane (TBCO), has been introduced as a potential replacement for the major use BRF, Hexabromocyclododecane (HBCD). However, little is known about effects of TBCO on aquatic organisms. Using zebrafish (Danio rerio) as a model species, objectives of this study were to determine whether TBCO has adverse effects on early life-stages and to investigate the molecular and biochemical mechanisms of any effects on development. Exposure to TBCO caused a concentration dependant increase in mortality, decrease in heart rate, and increase in incidences of spinal curvature and uninflated swim bladders. Neither peroxidation of lipids or mRNA abundances of genes important for the response to oxidative stress were greater in embryos exposed to TBCO suggesting effects were not caused by oxidative stress. The mRNA abundance of cytochrome p4501a was not greater in embryos exposed to TBCO suggesting that effects were not caused by activation of the aryl hydrocarbon receptor. Finally, mRNA abundances of genes important for development and inflation of the swim bladder were not affected by TBCO. Overall, TBCO causes adverse effects on early life-stages of zebrafish, but mechanisms of effects require further investigation.
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http://dx.doi.org/10.1016/j.chemosphere.2020.129195DOI Listing
March 2021

Effects of weathered sediment-bound dilbit on freshwater amphipods (Hyalella azteca).

Aquat Toxicol 2020 Nov 12;228:105630. Epub 2020 Sep 12.

Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, Canada.

Bitumen mined in the oil sands region of Northern Alberta, Canada, is diluted with natural gas condensates to form dilbit, which is transported through pipelines. Sections of these pipelines come close to freshwater ecosystems. If dilbit is spilled into or near an aquatic environment, environmental weathering processes, such as evaporation and sediment interaction, influence the fate and toxicity of dilbit to aquatic organisms. To date, most studies of the effects of dilbit on the health of aquatic organisms have not considered weathering processes. Thus, the goal of this study was to assess the toxicity of weathered sediment-bound dilbit (WSD) to an aquatic organism. Adult freshwater amphipods (Hyalella azteca) were exposed directly to WSD or the water-soluble fraction (WSF) of WSD. Direct exposure to WSD resulted in oil-mineral aggregates adhering to the appendages and gas exchange structures of amphipods, causing acute lethality. After a 10-min exposure to WSD, amphipods consumed half as much oxygen and their appendage movement was impaired. Exposure to the WSF, which contained a total PAH concentration of 1.08 μg/L, did not result in acute lethality, or significantly affect respiration, activity or acetylcholinesterase activity. Results of the present study indicate that physical interaction with oil-mineral aggregates after a spill of dilbit is a threat to benthic invertebrates, whereas the WSF does not cause acute adverse effects. As the transport of dilbit through pipelines increases in North America, studies must incorporate environmental weathering processes when determining the effects of dilbit on aquatic organisms.
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http://dx.doi.org/10.1016/j.aquatox.2020.105630DOI Listing
November 2020

Dicamba elevates concentrations of S-adenosyl methionine but does not induce oxidative stress or alter DNA methylation in rainbow trout (Oncorhynchus mykiss) hepatocytes.

Comp Biochem Physiol Part D Genomics Proteomics 2020 12 14;36:100744. Epub 2020 Sep 14.

Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, Canada; Water Institute for Sustainable Environments (WISE), University of Lethbridge, Lethbridge, Alberta, Canada. Electronic address:

Dicamba is a benzoic acid herbicide used to target woody and broadleaf weeds in industrial, domestic, and municipal spheres. Because of its widespread use, dicamba is frequently detected in surface waters near sites of application. However, little is known regarding the effects of dicamba on freshwater fishes. In the present study, primary cultures of hepatocytes from rainbow trout (Oncorhynchus mykiss) were exposed to either an environmentally relevant (0.22 or 2.2 μg L) or supra-environmental (22 μg L) concentration of dicamba for 48 h to investigate if oxidative stress is a mechanism of toxicity. mRNA abundances of genes involved in the response to oxidative stress, levels of lipid peroxidation, and concentrations of glutathione and s-adenosyl methionine (SAM) were quantified. Results indicate that dicamba does not induce oxidative stress. However, exposure to 2.2 μg L of dicamba did cause a 5.24-fold increase in concentrations of SAM. To investigate the mechanisms of increased SAM, effects of dicamba on global and genome-wide DNA methylation were quantified. Dicamba did not cause changes to DNA methylation. Overall, dicamba was not acutely toxic to hepatocytes and did not cause oxidative stress or changes in DNA methylation at environmentally relevant concentrations.
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http://dx.doi.org/10.1016/j.cbd.2020.100744DOI Listing
December 2020

Predicting Early Life Stage Mortality in Birds and Fishes from Exposure to Low-Potency Agonists of the Aryl Hydrocarbon Receptor: A Cross-Species Quantitative Adverse Outcome Pathway Approach.

Environ Toxicol Chem 2020 10 25;39(10):2055-2064. Epub 2020 Aug 25.

Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, Canada.

Dioxin-like compounds (DLCs) cause early life stage mortality of vertebrates through activation of the aryl hydrocarbon receptor (AhR). A prior study developed a cross-species quantitative adverse outcome pathway (qAOP) which can predict full dose-response curves of early life stage mortality for any species of bird or fish exposed to DLCs using the species- and chemical-specific 50% effect concentration (EC50) from an in vitro AhR transactivation assay with COS-7 cells. However, calculating a reliable EC50 for input into this qAOP requires the maximal response of the concentration-response curve to be known, which is not always possible for low-potency agonists, such as some polychlorinated biphenyls (PCBs). To enable predictions for these low-potency agonists, the present study revised this qAOP to use the effect concentration threshold (EC ) from the in vitro AhR transactivation assay as input. Significant linear relationships were demonstrated between EC and the dose to cause 0, 10, 50, or 100% mortality among early life stages of 3 species of birds and 7 species of fish for 4 DLCs: 2,3,7,8-tetrachlorodibenzo-p-dioxin, PCB 126, PCB 77, and PCB 105. These 4 linear relationships were combined to form the revised qAOP. This qAOP using the EC enables prediction of experimental dose-response curves for lower-potency agonists to within an order of magnitude on average, but the prior qAOP using EC50 predicts experimental dose-response curves for higher-potency agonists with greater accuracy. Environ Toxicol Chem 2020;39:2055-2064. © 2020 SETAC.
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http://dx.doi.org/10.1002/etc.4816DOI Listing
October 2020

Mechanisms of pH-Dependent Uptake of Ionizable Organic Chemicals by Fish from Oil Sands Process-Affected Water (OSPW).

Environ Sci Technol 2020 08 19;54(15):9547-9555. Epub 2020 Jul 19.

School of Environment and Sustainability (SENS), University of Saskatchewan, 44 Campus Drive, Saskatoon S7N 5C8, Canada.

Uptake and effects of ionizable organic chemicals (IOCs) that are weak acids in aqueous solution by fish can differ as a function of pH. While the pH-dependent behavior of select IOCs is well-understood, complex mixtures of IOCs, e.g., from oil sands process-affected water (OSPW), have not yet been studied systematically. Here, we established an in vitro screening method using the rainbow trout gill cell line, RTgill-W1, to investigate pH-dependent cytotoxicity and permeation of IOCs across cultured epithelia using ultra-high-performance liquid chromatography with high-resolution mass spectrometry (UPLC-HRMS). The assay was benchmarked using model chemicals and technical mixtures, and then used to characterize fractions and reconstituted extracts of field-collected OSPW. Significant pH-dependent cytotoxicity of individual IOCs, acidic fractions, and reconstituted extracts of OSPW was observed. In vitro data were in good agreement with data from a 96 h in vivo exposure experiment with juvenile rainbow trout. Permeation of some IOCs from OSPW was mediated by active transport, as revealed by studies in which inhibitors of these active transport mechanisms were applied. We conclude that the RTgill-W1 in vitro assay is useful for the screening of pH-dependent uptake of IOCs in fish, and has applications for in vitroin vivo extrapolation, and prioritization of chemicals in nontarget screenings.
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http://dx.doi.org/10.1021/acs.est.0c02522DOI Listing
August 2020

Influence of postexercise fasting on hunger and satiety in adults.

Appl Physiol Nutr Metab 2020 Sep 9;45(9):1022-1030. Epub 2020 Apr 9.

Department of Kinesiology and Physical Education, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada.

Research demonstrates that exercise acutely reduces appetite by stimulating the secretion of gut-derived satiety hormones. Currently there is a paucity of research examining the impact of postexercise nutrient intake on appetite regulation. The objective of this study was to examine how postexercise fasting versus feeding impacts the postexercise appetite response. In a randomized crossover intervention, 14 participants (body mass index: 26.9 ± 3.5 kg·m; age: 26.8 ± 6.7 years) received 1 of 2 recovery beverages: () water control (FAST) or () sweetened-milk (FED) after completing a 45-min (65%-70% peak oxygen uptake) evening exercise session (∼1900 h). Energy intake was assessed through a fasted ad libitum breakfast meal and 3-day food diaries. Perceived appetite was assessed using visual analogue scales. Appetite-regulating hormones glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY), and acyl-ghrelin were assessed pre-exercise, 1 h after exercise, and the morning following exercise. FAST increased subjective hunger compared with FED ( < 0.05). PYY and GLP-1 after exercise were decreased and acyl-ghrelin was increased in FAST, with these differences disappearing the day after exercise ( < 0.05). Ad libitum energy intake at breakfast the following morning did not differ between trials. Overall, in the absence of postexercise macronutrient consumption, there was a pronounced increase in objective and subjective appetite after exercise. The orexigenic effects of postexercise fasting, however, were not observed the morning following exercise. Postexercise fasting leads to reduced GLP-1 and PYY and increased hunger. Reduced GLP-1 and PYY after exercise is blunted by postexercise nutrient intake. Energy intake the day after exercise is not influenced by postexercise fasting.
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http://dx.doi.org/10.1139/apnm-2019-0947DOI Listing
September 2020

Effects of chemical fractions from an oil sands end-pit lake on reproduction of fathead minnows.

Chemosphere 2020 Jun 1;249:126073. Epub 2020 Feb 1.

Toxicology Centre, University of Saskatchewan, Saskatoon, SK, Canada; Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK, Canada; Department of Zoology and Center for Integrative Toxicology, Michigan State University, East Lansing, MI, USA; Department of Environmental Sciences, Baylor University, Waco, TX, USA. Electronic address:

Oil sands process-affected water (OSPW) is a byproduct of bitumen extraction in the surface-mining oil sands industry in Alberta, Canada. Organic compounds in OSPW can be acutely or chronically toxic to aquatic organisms, so part of a long-term strategy for remediation of OSPW is ageing of water in artificial lakes, termed end-pit lakes. BaseMine Lake (BML) is the first oil sands end-pit lake, commissioned in 2012. At the time of its establishment, an effects-directed analysis of BML-OSPW showed that naphthenic acids and polar organic chemical species containing sulfur or nitrogen contributed to its acute lethality. However, the chronic toxicity of these same chemical fractions has not yet been investigated. In this work, the short-term fathead minnow reproductive bioassay was used to assess endocrine-system effects of two fractions of BML-OSPW collected in 2015. One of the fractions (F1) contained predominantly naphthenic acids, while the other (F2) contained non-acidic polar organic chemical species. Exposure of minnows to F1 or F2 at concentrations equivalent to 25% (v/v) of the 2015 BML-OSPW sample (5-15% of the 2012 BML-OSPW sample) did not alter reproductive performance, fertilization success, or concentrations of sex steroids in female or male minnows. Additionally, there were no significant differences in fertility, hatching success, or incidence of morphological indices of embryos collected on day 7 or 14 from exposed breeding trios. However, exposure of male fathead minnow to 25% (v/v) intact 2015 BML-OSPW resulted in a significantly greater hepatosomatic index. Exposure of fathead minnow to refined fractions of dissolved organic chemicals in 2015 BML-OSPW, or a 25% (v/v) of the intact mixture did not affect fertility or fecundity as measured by use of the 21-day reproductive bioassay. These data will be useful in setting future threshold criteria for OSPW reclamation and treatment.
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http://dx.doi.org/10.1016/j.chemosphere.2020.126073DOI Listing
June 2020

Aryl hydrocarbon receptor nuclear translocators (ARNT1, ARNT2, and ARNT3) of white sturgeon (Acipenser transmontanus): Sequences, tissue-specific expressions, and response to β-naphthoflavone.

Comp Biochem Physiol C Toxicol Pharmacol 2020 May 17;231:108726. Epub 2020 Feb 17.

Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta T1K 3M4, Canada.

Sturgeons (Acipenseridae) are ancient fishes that have tissue-specific profiles of transcriptional responses to dioxin-like compounds (DLCs) that are unique from those generally measured in teleost fishes. Because DLCs exert their critical toxicities through activation of the aryl hydrocarbon receptor (AHR), this transcription factor has been the subject of intensive study. However, less attention has focused on the aryl hydrocarbon receptor nuclear translocator (ARNT), which is the dimerization partner of the AHR and required for AHR-mediated transcription. The present study sequenced ARNT1, ARNT2, and ARNT3 in a representative species of sturgeon, the white sturgeon (Acipenser transmontanus), and quantified tissue-specific basal transcript abundance for each ARNT and the response following exposure to the model agonist of the AHR, β-naphthoflavone. In common with other proteins in sturgeons, the amino acid sequences of ARNTs are more similar to those of tetrapods than are ARNTs of other fishes. Transcripts of ARNT1, ARNT2, and ARNT3 were detected in all tissues investigated. Expression of ARNTs are tightly regulated in vertebrates, but β-naphthoflavone caused down-regulation in liver and up-regulation in gill, while an upward trend was measured in intestine. ARNTs are dimeric partners for multiple proteins, including the hypoxia inducible factor 1α (HIF1α), which mediates response to hypoxia. A downward trend in abundance of HIF1α transcript was measured in liver of white sturgeon exposed to β-naphthoflavone. Altered expression of ARNTs and HIF1α caused by activation of the AHR might affect the ability of certain tissues in sturgeons to respond to hypoxia when co-exposed to DLCs or other agonists.
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http://dx.doi.org/10.1016/j.cbpc.2020.108726DOI Listing
May 2020

Teamwork and safety climate affect antimicrobial stewardship for asymptomatic bacteriuria.

Infect Control Hosp Epidemiol 2019 09 24;40(9):963-967. Epub 2019 Jul 24.

Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey Veterans Affairs Medical Center,Houston,Texas.

Objective: In preparation for a multisite antibiotic stewardship intervention, we assessed knowledge and attitudes toward management of asymptomatic bacteriuria (ASB) plus teamwork and safety climate among providers, nurses, and clinical nurse assistants (CNAs).

Design: Prospective surveys during January-June 2018.

Setting: All acute and long-term care units of 4 Veterans' Affairs facilities.

Methods: The survey instrument included 2 previously tested subcomponents: the Kicking CAUTI survey (ASB knowledge and attitudes) and the Safety Attitudes Questionnaire (SAQ).

Results: A total of 534 surveys were completed, with an overall response rate of 65%. Cognitive biases impacting management of ASB were identified. For example, providers presented with a case scenario of an asymptomatic patient with a positive urine culture were more likely to give antibiotics if the organism was resistant to antibiotics. Additionally, more than 80% of both nurses and CNAs indicated that foul smell is an appropriate indication for a urine culture. We found significant interprofessional differences in teamwork and safety climate (defined as attitudes about issues relevant to patient safety), with CNAs having highest scores and resident physicians having the lowest scores on self-reported perceptions of teamwork and safety climates (P < .001). Among providers, higher safety-climate scores were significantly associated with appropriate risk perceptions related to ASB, whereas social norms concerning ASB management were correlated with higher teamwork climate ratings.

Conclusions: Our survey revealed substantial misunderstanding regarding management of ASB among providers, nurses, and CNAs. Educating and empowering these professionals to discourage unnecessary urine culturing and inappropriate antibiotic use will be key components of antibiotic stewardship efforts.
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http://dx.doi.org/10.1017/ice.2019.176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474408PMC
September 2019

A Cross-species Quantitative Adverse Outcome Pathway for Activation of the Aryl Hydrocarbon Receptor Leading to Early Life Stage Mortality in Birds and Fishes.

Environ Sci Technol 2018 07 19;52(13):7524-7533. Epub 2018 Jun 19.

Toxicology Centre , University of Saskatchewan , Saskatoon , Saskatchewan S7N 5B3 , Canada.

Dioxin-like compounds (DLCs) elicit adverse effects through activation of the aryl hydrocarbon receptor (AHR). Prior investigations demonstrated that sensitivity to activation of AHR1 in an in vitro AHR transactivation assay is predictive of early life stage mortality among birds. The present study investigated the link between sensitivity to activation of AHR1s and AHR2s and early life stage mortality among fishes. A significant, linear relationship was demonstrated between sensitivity to activation of AHR2 and early life stage mortality among nine fishes, while no relationship was found for AHR1. The slope and y-intercept for the linear relationship between sensitivity to activation of AHR1 and early life stage mortality in birds was not statistically different from the same relationship for AHR2 in fishes. Data for fishes and birds across DLCs were expanded into four significant, linear regression models describing the relationship between sensitivity to activation of AHR and the dose to cause early life stage mortality of 0%, 10%, 50%, or 100%. These four relationships were combined to form a quantitative adverse outcome pathway which can predict dose-response curves of early life stage mortality for DLCs to any bird or fish from species- and chemical-specific responses in an in vitro AHR transactivation assay.
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http://dx.doi.org/10.1021/acs.est.8b01438DOI Listing
July 2018

Combining High-Throughput Sequencing of sedaDNA and Traditional Paleolimnological Techniques To Infer Historical Trends in Cyanobacterial Communities.

Environ Sci Technol 2018 06 5;52(12):6842-6853. Epub 2018 Jun 5.

Toxicology Centre , University of Saskatchewan , Saskatoon , Saskatchewan S7N 5B3 , Canada.

Freshwaters worldwide are under increasing pressure from anthropogenic activities and changing climate. Unfortunately, many inland waters lack sufficient long-term monitoring to assess environmental trends. Analysis of sedimentary ancient DNA ( sedaDNA) is emerging as a means to reconstruct the past occurrence of microbial communities of inland waters. The purpose of this study was to assess a combination of high-throughput sequencing (16S rRNA) of sedaDNA and traditional paleolimnological analyses to explore multidecadal relationships among cyanobacterial community composition, the potential for cyanotoxin production, and paleoenvironmental proxies. DNA was extracted from two sediment cores collected from a northern Canadian Great Plains reservoir. Diversity indices illustrated significant community-level changes since reservoir formation. Furthermore, higher relative abundances in more recent years were observed for potentially toxic cyanobacterial genera including Dolichospermum. Correlation-based network analysis revealed this trend significantly and positively correlated to abundances of the microcystin synthetase gene ( mcyA) and other paleoproxies (nutrients, pigments, stanols, sterols, and certain diatom species), demonstrating synchrony between molecular and more standard proxies. These findings demonstrate a novel approach to infer long-term dynamics of cyanobacterial diversity in inland waters and highlight the power of high-throughput sequencing to reconstruct trends in environmental quality and inform lake and reservoir management and monitoring program design.
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http://dx.doi.org/10.1021/acs.est.7b06386DOI Listing
June 2018

Protocol to disseminate a hospital-site controlled intervention using audit and feedback to implement guidelines concerning inappropriate treatment of asymptomatic bacteriuria.

Implement Sci 2018 01 19;13(1):16. Epub 2018 Jan 19.

Center for Innovations in Quality, Effectiveness, and Safety (IQuESt) (152), Michael E. DeBakey Veterans Affairs Medical Center, 2002 Holcombe Boulevard, Houston, TX, 77030, USA.

Background: Antimicrobial stewardship to combat the spread of antibiotic-resistant bacteria has become a national priority. This project focuses on reducing inappropriate use of antimicrobials for asymptomatic bacteriuria (ASB), a very common condition that leads to antimicrobial overuse in acute and long-term care. We previously conducted a successful intervention, entitled "Kicking Catheter Associated Urinary Tract Infection (CAUTI): the No Knee-Jerk Antibiotics Campaign," to decrease guideline-discordant ordering of urine cultures and antibiotics for ASB. The current objective is to facilitate implementation of a scalable version of the Kicking CAUTI campaign across four geographically diverse Veterans Health Administration facilities while assessing what aspects of an antimicrobial stewardship intervention are essential to success and sustainability.

Methods: This project uses an interrupted time series design with four control sites. The two main intervention tools are (1) an evidence-based algorithm that distills the guidelines into a streamlined clinical pathway and (2) case-based audit and feedback to train clinicians to use the algorithm. Our conceptual framework for the development and implementation of this intervention draws on May's General Theory of Implementation. The intervention is directed at providers in acute and long-term care, and the goal is to reduce inappropriate screening for and treatment of ASB in all patients and residents, not just those with urinary catheters. The start-up for each facility consists of centrally-led phone calls with local site champions and baseline surveys. Case-based audit and feedback will begin at a given site after the start-up period and continue for 12 months, followed by a sustainability assessment. In addition to the clinical outcomes, we will explore the relationship between the dose of the intervention and clinical outcomes.

Discussion: This project moves from a proof-of-concept effectiveness study to implementation involving significantly more sites, and uses the General Theory of Implementation to embed the intervention into normal processes of care with usual care providers. Aspects of implementation that will be explored include dissemination, internal and external facilitation, and organizational partnerships. "Less is More" is the natural next step from our prior successful Kicking CAUTI intervention, and has the potential to improve patient care while advancing the science of implementation.
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http://dx.doi.org/10.1186/s13012-018-0709-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5775527PMC
January 2018

Elucidating mechanisms of toxic action of dissolved organic chemicals in oil sands process-affected water (OSPW).

Chemosphere 2017 Nov 8;186:893-900. Epub 2017 Aug 8.

Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada; State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023, China; Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada; Zoology Department, Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824, USA; School of Biological Sciences, University of Hong Kong, 999077, Hong Kong Special Administrative Region. Electronic address:

Oil sands process-affected water (OSPW) is generated during extraction of bitumen in the surface-mining oil sands industry in Alberta, Canada, and is acutely and chronically toxic to aquatic organisms. It is known that dissolved organic compounds in OSPW are responsible for most toxic effects, but knowledge of the specific mechanism(s) of toxicity, is limited. Using bioassay-based effects-directed analysis, the dissolved organic fraction of OSPW has previously been fractionated, ultimately producing refined samples of dissolved organic chemicals in OSPW, each with distinct chemical profiles. Using the Escherichia coli K-12 strain MG1655 gene reporter live cell array, the present study investigated relationships between toxic potencies of each fraction, expression of genes and characterization of chemicals in each of five acutely toxic and one non-toxic extract of OSPW derived by use of effects-directed analysis. Effects on expressions of genes related to response to oxidative stress, protein stress and DNA damage were indicative of exposure to acutely toxic extracts of OSPW. Additionally, six genes were uniquely responsive to acutely toxic extracts of OSPW. Evidence presented supports a role for sulphur- and nitrogen-containing chemical classes in the toxicity of extracts of OSPW.
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http://dx.doi.org/10.1016/j.chemosphere.2017.08.025DOI Listing
November 2017

Identification of Chemicals that Cause Oxidative Stress in Oil Sands Process-Affected Water.

Environ Sci Technol 2017 Aug 17;51(15):8773-8781. Epub 2017 Jul 17.

Department of Biological Sciences, University of Lethbridge , Lethbridge, Alberta T1K 3M4, Canada.

Oil sands process-affected water (OSPW) has been reported to cause oxidative stress in organisms, yet the causative agents remain unknown. In this study, a high-throughput in vitro Nrf2 reporter system was used, to determine chemicals in OSPW that cause oxidative stress. Five fractions, with increasing polarity, of the dissolved organic phase of OSPW were generated by use of solid phase extraction cartridges. The greatest response of Nrf2 was elicited by F2 (2.7 ± 0.1-fold), consistent with greater hydroperoxidation of lipids in embryos of Japanese medaka (Oryzias latipes) exposed to F2. Classic naphthenic acids were mainly eluted in F1, and should not be causative chemicals. When F2 was fractionated into 60 subfractions by use of HPLC, significant activation of Nrf2 was observed in three grouped fractions: F2.8 (1.30 ± 0.01-fold), F2.16 (1.34 ± 0.05-fold), and F2.25 (1.28 ± 0.15-fold). 54 compounds were predicted to be potential chemicals causing Nrf2 response, predominated by SO and O species. By use of high-resolution MS spectra, these SO and O species were identified as hydroxylated aldehydes. This study demonstrated that polyoxygenated chemicals, rather than classic NAs, were the major chemicals responsible for oxidative stress in the aqueous phase of OSPW.
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http://dx.doi.org/10.1021/acs.est.7b01987DOI Listing
August 2017

Hydroxylated 2-Ethylhexyl tetrabromobenzoate isomers in house dust and their agonistic potencies with several nuclear receptors.

Environ Pollut 2017 Aug 13;227:578-586. Epub 2017 May 13.

Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, SK, S7N 5B3, Canada; Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK, S7N 5B3, Canada; Zoology Department, Center for Integrative Toxicology, Michigan State University, East Lansing, MI, USA; Department of Biology and Chemistry, City University of Hong Kong, Kowloon, People's Republic of China; School of Biological Sciences, University of Hong Kong, People's Republic of China; State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, People's Republic of China.

In the current study, by combining ultra-high resolution (UHR) MS spectra, MS spectra, and derivatization, three hydroxylated isomers of 2-ethylhexyl tetrabromobenzoate (OH-TBB) were identified in Firemaster 550 and BZ-54 technical products. Also, a new LC-UHRMS method, using atmospheric pressure chemical ionization (APCI), was developed for simultaneous analysis of OH-TBB, TBB, hydroxylated bis(2-ethylhexyl)-tetrabromophthalate (OH-TBPH) and TBPH in 23 samples of dust collected from houses in Saskatoon, SK, Canada. OH-TBBs were detected in 91% of samples, with a geometric mean concentration of 0.21 ng/g, which was slightly less than those of OH-TBPH (0.35 ng/g). TBB was detected in 100% of samples of dust with a geometric mean concentration of 992 ng/g. Significant (p < 0.001) log-linear relationships between concentrations of OH-TBBs, TBB, or OH-TBPHs and TBPH in dust support the hypothesis of a common source of these compounds. OH-TBBs were found to be strong agonists of peroxisome proliferator-activated receptor gamma (PPARγ) and weaker agonists of the estrogen receptor (ER), but no agonistic potencies was observed with the androgen receptor (AR). Occurrence of OH-TBBs in technical products and house dust, together with their relatively strong PPARγ potencies, indicated their potential risk to health of humans.
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http://dx.doi.org/10.1016/j.envpol.2017.04.094DOI Listing
August 2017

Effects of chronic exposure to dietary selenomethionine on the physiological stress response in juvenile white sturgeon (Acipenser transmontanus).

Aquat Toxicol 2017 May 3;186:77-86. Epub 2017 Feb 3.

Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3, Canada; School of Environment and Sustainability, University of Saskatchewan, Saskatoon, SK, S7N 5C8, Canada. Electronic address:

Selenium (Se) is an essential micronutrient, but at low concentrations can be toxic to aquatic organisms. Selenomethionine (SeMeth) is the primary dietary form of Se aquatic organisms are exposed to and is an environmental concern because it persists and bioaccumulates. White sturgeon (WS) might be particularly susceptible to bioaccumulative toxicants, such as SeMeth, due to their longevity and benthic lifestyle. Se exposure is known to have adverse effects on the physiological stress response in teleosts, but these effects are unknown in WS. Therefore, the goal of this study was to determine effects of dietary SeMeth on the ability of WS to mount a stress response. Juvenile WS were administered food spiked with 1.4, 5.6, 22.4 and 104.4μg Se/g dry mass (dm) for 72days. Lower doses were chosen to represent environmentally relevant concentrations, while the high dose represented a worst case scenario exposure. On day 72, fish were subjected to a 2min handling stressor, and they were sampled at 0, 2 and 24h post-stressor. Cortisol, glucose and lactate concentrations were quantified in blood plasma and glycogen concentrations were quantified in muscle and liver. Transcript abundance of genes involved in corticosteroidogenesis and energy metabolism were determined using qPCR. Under basal conditions, WS fed 104.4μg Se/g dm had significantly greater concentrations of plasma cortisol and lactate, and significantly lower concentrations of plasma glucose and liver glycogen, compared to controls. Corticosteroid 11-beta dehydrogenase 2 (hsd11b2) abundance was lower in WS fed 22.4 and 104.4μg Se/g dm, indicating less conversion of cortisol to cortisone. Abundance of the glucocorticoid receptor (gcr) was significantly lower in high dose WS, suggesting lower tissue sensitivity to glucocorticoids. The increasing trend in phosphoenolpyruvate carboxykinase (pepck) abundance, with increasing SeMeth exposure, was consistent with greater cortisol and glucose concentrations in high dose WS. Exposure to an acute handling stressor elicited a typical cortisol response, but the magnitude of the response appeared to be significantly lower than those typically observed in teleosts. SeMeth also did not appear to modulate the cortisol response to a secondary stressor. However, WS exposed to 22.4μg Se/g dm and sampled 2h post-stressor, had significantly higher concentrations of muscle glycogen compared to controls, indicating effects on their ability to utilize muscle glycogen for energy. Overall, the results indicate that chronic exposure to dietary SeMeth concentrations >22.4μg/g can affect cortisol dynamics and mobilization of energy substrates in juvenile WS.
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http://dx.doi.org/10.1016/j.aquatox.2017.02.003DOI Listing
May 2017

Toward understanding the impacts of sediment contamination on a native fish species: transcriptional effects, EROD activity, and biliary PAH metabolites.

Environ Sci Eur 2016 5;28(1):28. Epub 2016 Dec 5.

Department of Ecosystem Analysis, Institute for Environmental Research, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany ; School of Environment and Sustainability, University of Saskatchewan, 44 Campus Drive, Saskatoon, SK S7N 5B3 Canada.

Background: Both frequency and intensity of flood events are expected to increase as a result of global climate change in the upcoming decades, potentially resulting in increased re-suspension of sediments in fluvial systems. Contamination of these re-suspended sediments with legacy contaminants, including dioxins and dioxin-like compounds (DLCs), as well as polycyclic aromatic hydrocarbons (PAHs) is of great ecotoxicological concern. DLCs, and to some extent also PAHs, exhibit their toxicity through activation of the aryl hydrocarbon receptor (AhR). However, interactions of DLCs with pathways other than those known to be mediated through the AhR are not fully understood to date.

Methods: This study aimed to investigate molecular and biochemical effects in roach ( during a 10 days exposure to suspensions of three natural sediments that differed in the level of DLC contamination. Concentrations of biliary PAH metabolites and hepatic 7-ethoxyresorufin--deethylase activity were quantified in exposed fish. Furthermore, the abundance of transcripts of several genes related to energy metabolism, response to oxidative stress, and apoptosis, as well as cytochrome P450 1A () was quantified.

Results: Biliary PAH metabolites and activation of the AhR were confirmed as suitable early warning biomarkers of exposure to suspended sediments containing DLCs and PAHs that corresponded well with analytically determined concentrations of those contaminants. Although the abundances of transcripts of superoxide dismutase (), protein kinase c delta (), and ATP-binding cassette transporter c9 ( were altered by the treatment compared with unexposed control fish, none of these showed a time- or concentration-dependent response. The abundance of transcripts of pyruvate carboxylase () and transferrin variant d () remained unaltered by the treatments.

Conclusions: We have shown that contaminated sediments can become a risk for fish during re-suspension events (e.g., flooding and dredging). We have also demonstrated that roach, which are native to most European freshwater systems, are suitable sentinel species due to their great sensitivity and ecological relevance. Roach may be particularly suitable in future field studies to assess the toxicological concerns associated with the release of DLCs and PAHs during sediment re-suspension.
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http://dx.doi.org/10.1186/s12302-016-0096-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136570PMC
December 2016

Toxicokinetics and toxicodynamics of chlorpyrifos is altered in embryos of Japanese medaka exposed to oil sands process-affected water: evidence for inhibition of P-glycoprotein.

J Appl Toxicol 2017 05 24;37(5):591-601. Epub 2016 Oct 24.

Toxicology Centre, University of Saskatchewan, Saskatoon, SK, Canada.

Oil sands process-affected water (OSPW) is generated during extraction of bitumen in the surface mining oil sands industry in Alberta, Canada. Studies were performed in vitro by use of Caco-2 cells, and in vivo with larvae of Japanese medaka (Oryzias latipes) to determine if organic compounds from the aqueous phase of OSPW inhibit ATP binding cassette protein ABCB1 (permeability-glycoprotein, P-gp). Neutral and basic fractions of OSPW inhibited activity of P-gp in Caco-2 cells by 1.9- and 2.0-fold, respectively, while the acidic fraction had the least effect. The organophosphate pesticides chlorpyrifos (a substrate of P-gp) and malathion (not a substrate of P-gp), were used as model chemicals to investigate inhibition of P-gp in larvae. Co-exposure to chlorpyrifos and an extract of OSPW containing basic and neutral compounds reduced survival of larvae to 26.5% compared to survival of larvae exposed only to chlorpyrifos, which was 93.7%. However, co-exposure to malathion and the extract of OSPW did not cause acute lethality compared to exposure only to malathion. Accumulation and bioconcentration of chlorpyrifos, but not malathion, was greater in larvae co-exposed with the extract of OSPW. The terminal elimination half-life of chlorpyrifos in larvae exposed to chlorpyrifos in freshwater was 5 days compared with 11.3 days in larvae exposed to chlorpyrifos in OSPW. Results suggest that in non-acute exposures, basic and neutral organic compounds in the water-soluble fraction of OSPW inhibit activity of P-gp, which suggests that OSPW has the potential to cause adverse effects by chemosensitization. Copyright © 2016 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/jat.3397DOI Listing
May 2017

Untargeted Screening and Distribution of Organo-Iodine Compounds in Sediments from Lake Michigan and the Arctic Ocean.

Environ Sci Technol 2016 09 9;50(18):10097-105. Epub 2016 Sep 9.

Toxicology Centre, University of Saskatchewan , 44 Campus Drive, Saskatoon, Saskatchewan S7N 5B3, Canada.

The majority of halogenated organic compounds present in the environment remain unidentified. To address this data gap, we recently developed an untargeted method (data-independent precursor isolation and characteristic fragment; DIPIC-Frag) for identification of unknown organo-bromine compounds. In this study, the method was adapted to enable untargeted screening of natural and synthetic organo-iodine compounds (NSOICs) in sediments. A total of 4,238 NSOIC peaks were detected in sediments from Lake Michigan. Precursor ions and formulas were determined for 2,991 (71%) of the NSOIC peaks. These compounds exhibited variations in abundances (<10(3) to ∼10(7)), m/z values (206.9304-996.9474), retention times (1.0-29.7 min), and number of iodine atoms (1-4). Hierarchical cluster analysis showed that sediments in closer proximity exhibited similar profiles of NSOICs. NSOICs were screened in 10 samples of sediment from the Arctic Ocean to compare the profiles of NSOICs between freshwater and marine sediments. A total of 3,168 NSOIC peaks were detected, and profiles of NSOICs in marine sediments were clearly distinct from Lake Michigan. The coexistence of brominated and iodinated analogues indicated that some NSOICs are of natural origin. Different ratios of abundances of iodinated compounds to brominated analogues were observed and proposed as a marker to distinguish sources of NSOICs.
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http://dx.doi.org/10.1021/acs.est.6b03221DOI Listing
September 2016

Linking Oxidative Stress and Magnitude of Compensatory Responses with Life-Stage Specific Differences in Sensitivity of White Sturgeon (Acipenser transmontanus) to Copper or Cadmium.

Environ Sci Technol 2016 09 24;50(17):9717-26. Epub 2016 Aug 24.

School of Environment and Sustainability, University of Saskatchewan , Saskatoon, SK S7N 5C8, Canada.

Sensitivity of white sturgeon (Acipenser transmontanus) to copper (Cu) or cadmium (Cd) has been shown to significantly differ as a function of life-stage. This study investigated oxidative stress, metal homeostasis, and associated compensatory responses as potential mechanisms of this sensitivity pattern in three early life-stages. Sturgeon were most sensitive to Cu at 15 days post hatch (dph), which was accompanied by a significant increase in lipid peroxidation (LPO). Genes involved with amelioration of oxidative stress were significantly less inducible at this stage than in older, less sensitive fry. At 48 dph, acute lethality of sturgeon exposed to Cd was greatest and body LPO was significantly induced by 3.5-fold at 5 μg Cd/L. Moreover, there was a small but significant increase in antioxidative responses. At 139 dph, sturgeon were most tolerant to Cu and Cd and accumulation of these metals was least. Also, expression of metallothionein (MT) and apoptotic genes were greatest while expression of metal transporters was reduced and concentration of LPO was not different from controls. Our results suggest that life-stage specific sensitivity of white sturgeon to metals is complex, encompassing differences in the ability to mount compensatory responses important for metal homeostasis and combating oxidative stress and concomitant damages.
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http://dx.doi.org/10.1021/acs.est.6b03301DOI Listing
September 2016

Is hepatic oxidative stress a main driver of dietary selenium toxicity in white sturgeon (Acipenser transmontanus)?

Ecotoxicol Environ Saf 2016 Nov 3;133:334-40. Epub 2016 Aug 3.

School of Environment and Sustainability, University of Saskatchewan, Room 323, Kirk Hall, 117 Science Place, Saskatoon, Saskatchewan, Canada S7N 5C8; Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, Saskatchewan, Canada S7N 5B3. Electronic address:

Most species of sturgeon have experienced significant population declines and poor recruitment over the past decades, leading many, including white sturgeon (Acipenser transmontanus), to be listed as endangered. Reasons for these declines are not yet fully understood but benthic lifestyle, longevity, and delayed sexual maturation likely render sturgeon particularly susceptible to factors such as habitat alteration and contaminant exposures. One contaminant of particular concern to white sturgeon is selenium (Se), especially in its more bioavailable form selenomethionine (SeMet), as it is known to efficiently bioaccumulate in prey items of this species. Studies have shown white sturgeon to be among the most sensitive species of fish to dietary SeMet as well as other pollutants such as metals, dioxin-like chemicals and endocrine disrupters. One of the primary hypothesized mechanisms of toxicity of SeMet in fish is oxidative stress; however, little is know about the specific mode by which SeMet affects the health of white sturgeon. Therefore, the aim of this study was to characterize oxidative stress and associated antioxidant responses as a molecular event of toxicity, and to link it with the pathological effects observed previously. Specifically, three-year-old white sturgeon were exposed for 72 days via their diet to 1.4, 5.6, 22.4 or 104.4µg Se per g feed (dm). Doses were chosen to range over a necessary Se intake level, current environmentally relevant intakes and an intake representing predicted increases of Se release. Lipid hydroperoxides, which are end products of lipid oxidation, were quantified as a marker of oxidative stress. Changes in gene expression of glutathione peroxidase (GPx), superoxide dismutase, catalase, glutathione S-transferase, apoptosis inducing factor and caspase 3 were quantified as markers of the response to oxidative stress. Concentrations of lipid hydroperoxides were highly variable within dose groups and no dose response was observed. GPx expression was significantly increased in the low dose group indicating an induced antioxidant response. Expression of other genes were not significantly induced or suppressed. Overall, there was very little evidence of oxidative stress, and therefore, in contrast to previous reports on other species of teleost fishes, oxidative stress is not believed to be a main driver of toxicity in white sturgeon exposed to SeMet.
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http://dx.doi.org/10.1016/j.ecoenv.2016.07.004DOI Listing
November 2016

Effect of Lipid Partitioning on Predictions of Acute Toxicity of Oil Sands Process Affected Water to Embryos of Fathead Minnow (Pimephales promelas).

Environ Sci Technol 2016 08 28;50(16):8858-66. Epub 2016 Jul 28.

Toxicology Centre, University of Saskatchewan , Saskatoon, Saskatchewan S7N 5A2, Canada.

Dissolved organic compounds in oil sands process affected water (OSPW) are known to be responsible for most of its toxicity to aquatic organisms, but the complexity of this mixture prevents use of traditional bottom-up approaches for predicting toxicities of mixtures. Therefore, a top-down approach to predict toxicity of the dissolved organic fraction of OSPW was developed and tested. Accurate masses (i.e., m/z) determined by ultrahigh resolution mass spectrometry in negative and positive ionization modes were used to assign empirical chemical formulas to each chemical species in the mixture. For each chemical species, a predictive measure of lipid accumulation was estimated by stir-bar sorptive extraction (SBSE) to poly(dimethyl)siloxane, or by partitioning to solid-supported lipid membranes (SSLM). A narcosis mode of action was assumed and the target-lipid model was used to estimate potencies of mixtures by assuming strict additivity. A model developed using a combination of the SBSE and SSLM lipid partitioning estimates, whereby the accumulation of chemicals to neutral and polar lipids was explicitly considered, was best for predicting empirical values of LC50 in 96-h acute toxicity tests with embryos of fathead minnow (Pimephales promelas). Model predictions were within 4-fold of observed toxicity for 75% of OSPW samples, and within 8.5-fold for all samples tested, which is comparable to the range of interlaboratory variability for in vivo toxicity testing.
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http://dx.doi.org/10.1021/acs.est.6b01481DOI Listing
August 2016

Peroxisome Proliferator-Activated Receptor γ is a Sensitive Target for Oil Sands Process-Affected Water: Effects on Adipogenesis and Identification of Ligands.

Environ Sci Technol 2016 07 11;50(14):7816-24. Epub 2016 Jul 11.

Toxicology Centre, University of Saskatchewan , 44 Campus Drive, Saskatoon, Saskatchewan Canada , S7N 5B3.

Identification of toxic components of complex mixtures is a challenge. Here, oil sands process-affected water (OSPW) was used as a case study to identify those toxic components with a known protein target. Organic chemicals in OSPW exhibited dose-dependent activation of peroxisome proliferator-activated receptor γ (PPARγ) at concentrations less than those currently in the environment (0.025× equivalent of full-strength OSPW), by use of a luciferase reporter gene assay. Activation of PPARγ-mediated adipogenesis by OSPW was confirmed in 3T3L1 preadipocytes, as evidenced by accumulation of lipids and up-regulation of AP2, LPL, and PPARγ gene expression after exposure to polar fractions of OSPW. Unexpectedly, the nonpolar fractions of OSPW inhibited differentiation of preadipocytes via activation of the Wnt signaling pathway. Organic chemicals in OSPW that were ligands of PPARγ were identified by use of a pull-down system combined with untargeted chemical analysis (PUCA), with a recombinant PPARγ protein. Thirty ligands of PPARγ were identified by use of the PUCA assay. High resolution MS(1) and MS(2) spectra were combined to predict the formulas or structures of a subset of ligands, and polyoxygenated or heteroatomic chemicals, especially hydroxylated carboxylic/sulfonic acids, were the major ligands of PPARγ.
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http://dx.doi.org/10.1021/acs.est.6b01890DOI Listing
July 2016

Combined Transcriptomic and Proteomic Approach to Identify Toxicity Pathways in Early Life Stages of Japanese Medaka (Oryzias latipes) Exposed to 1,2,5,6-Tetrabromocyclooctane (TBCO).

Environ Sci Technol 2016 07 11;50(14):7781-90. Epub 2016 Jul 11.

Toxicology Centre, University of Saskatchewan , Saskatoon, Saskatchewan S7N 5B3, Canada.

Currently, the novel brominated flame retardant 1,2,5,6-tetrabromocyclooctane (TBCO) is considered a potential replacement for hexabromocyclododecane (HBCD). Therefore, use of TBCO could increase in the near future. To assess potential toxicological risks to aquatic organisms, embryos of Japanese medaka (Oryzias latipes) were exposed to 10, 100, or 1000 μg/L TBCO from 2 h postfertilization until 1 day post-hatch. TBCO accumulated in embryos in the order of 0.43-1.3 × 10(4)-fold, and the rate constant of accumulation was 1.7-1.8 per day. The number of days to hatch and the hatching success of embryos exposed to the medium and the greatest concentrations of TBCO were impaired. Responses of the transcriptome (RNA-seq) and proteome were characterized in embryos exposed to 100 μg/L TBCO because this was the least concentration of TBCO that caused an effect on hatching. Consistent with effects on hatching, proteins whose abundances were reduced by exposure to TBCO were enriched in embryo development and hatching pathways. Also, on the basis of the responses of transcriptome and proteome, it was predicted that TBCO might impair vision and contraction of cardiac muscle, respectively, and these effects were confirmed by targeted bioassays. This study provided a comprehensive understanding of effects of TBCO on medaka at early life stages and illustrated the power of "omics" to explain and predict phenotypic responses to chemicals.
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http://dx.doi.org/10.1021/acs.est.6b01249DOI Listing
July 2016

Bioconcentration of Dissolved Organic Compounds from Oil Sands Process-Affected Water by Medaka (Oryzias latipes): Importance of Partitioning to Phospholipids.

Environ Sci Technol 2016 06 9;50(12):6574-82. Epub 2016 Jun 9.

Division of Analytical & Environmental Toxicology, Department of Laboratory Medicine & Pathology, University of Alberta , 10-102 Clinical Sciences Building, Edmonton, Alberta, Canada , T6G 2G3.

The complex mixture of dissolved organics in oil sands process-affected water (OSPW) is acutely lethal to fish at environmentally relevant concentrations, but few bioconcentration factors (BCFs) have been measured for its many chemical species. Japanese medaka (Oryzias latipes) were exposed to 10% OSPW, and measured BCFs were evaluated against predicted BCFs from octanol-water distribution ratios (DOW) and phospholipid membrane-water distribution ratios (DMW). Two heteroatomic chemical classes detected in positive ion mode (SO(+), NO(+)) and one in negative mode (O2(-), also known as naphthenic acids) had the greatest DMW values, as high as 10 000. Estimates of DMW were similar to and correlated with DOW for O(+), O2(+), SO(+), and NO(+) chemical species, but for O2(-) and SO2(-) species the DMW values were much greater than the corresponding DOW, suggesting the importance of electrostatic interactions for these ionizable organic acids. Only SO(+), NO(+), and O2(-) species were detectable in medaka exposed to OSPW, and BCFs for SO(+) and NO(+) species ranged from 0.6 to 28 L/kg, lower than predicted (i.e., 1.4-1.7 × 10(3) L/kg), possibly because of biotransformation of these hydrophobic substances. BCFs of O2(-) species ranged from 0.7 to 53 L/kg, similar to predicted values and indicating that phospholipid partitioning was an important bioconcentration mechanism.
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http://dx.doi.org/10.1021/acs.est.6b01354DOI Listing
June 2016
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