Using Domestic and Free-Ranging Arctic Canid Models for Environmental Molecular Toxicology Research.

The use of sentinel species for population and ecosystem health assessments has been advocated as part of a One Health perspective. The Arctic is experiencing rapid change, including climate and environmental shifts, as well as increased resource development, which will alter exposure of biota to environmental agents of disease. Arctic canid species have wide geographic ranges and feeding ecologies and are often exposed to high concentrations of both terrestrial and marine-based contaminants. The domestic dog (Canis lupus familiaris) has been used in biomedical research for a number of years and has been advocated as a sentinel for human health due to its proximity to humans and, in some instances, similar diet. Exploiting the potential of molecular tools for describing the toxicogenomics of Arctic canids is critical for their development as biomedical models as well as environmental sentinels. Here, we present three approaches analyzing toxicogenomics of Arctic contaminants in both domestic and free-ranging canids (Arctic fox, Vulpes lagopus). We describe a number of confounding variables that must be addressed when conducting toxicogenomics studies in canid and other mammalian models. The ability for canids to act as models for Arctic molecular toxicology research is unique and significant for advancing our understanding and expanding the tool box for assessing the changing landscape of environmental agents of disease in the Arctic.

[1]  T. O'hara,et al.  Mercury, selenium and fish oils in marine food webs and implications for human health , 2015, Journal of the Marine Biological Association of the United Kingdom.

[2]  T. O'hara,et al.  Evaluating the effect of ambient particulate pollution on DNA methylation in Alaskan sled dogs: potential applications for a sentinel model of human health. , 2015, The Science of the total environment.

[3]  Matthew E. Ritchie,et al.  limma powers differential expression analyses for RNA-sequencing and microarray studies , 2015, Nucleic acids research.

[4]  M. Salman,et al.  Mercury in gray wolves (Canis lupus) in Alaska: increased exposure through consumption of marine prey. , 2014, The Science of the total environment.

[5]  R. Dietz,et al.  Size and density of East Greenland polar bear (Ursus maritimus) skulls: Valuable bio-indicators of environmental changes? , 2013 .

[6]  H. Chan,et al.  Body burden of metals and persistent organic pollutants among Inuit in the Canadian Arctic. , 2013, Environment international.

[7]  Natalie L. M. Cappaert,et al.  Delay and impairment in brain development and function in rat offspring after maternal exposure to methylmercury. , 2013, Toxicological sciences : an official journal of the Society of Toxicology.

[8]  R. Dietz,et al.  What are the toxicological effects of mercury in Arctic biota? , 2013, The Science of the total environment.

[9]  Rolf Altenburger,et al.  Mixture toxicity revisited from a toxicogenomic perspective. , 2012, Environmental science & technology.

[10]  J. Castellini,et al.  Toxicokinetics of mercury in blood compartments and hair of fish-fed sled dogs , 2011, Acta veterinaria Scandinavica.

[11]  T. Larson,et al.  DIESEL particulate exposed macrophages alter endothelial cell expression of eNOS, iNOS, MCP1, and glutathione synthesis genes. , 2011, Toxicology in vitro : an international journal published in association with BIBRA.

[12]  D. Boyd,et al.  Blood-based biomarkers of selenium and thyroid status indicate possible adverse biological effects of mercury and polychlorinated biphenyls in Southern Beaufort Sea polar bears. , 2011, Environmental research.

[13]  T. O'hara,et al.  Adaptation of mammalian host-pathogen interactions in a changing arctic environment , 2011, Acta veterinaria Scandinavica.

[14]  T. Nicolson,et al.  The Post-Transcriptional Regulator EIF2S3 and Gender Differences in the Dog: Implications for Drug Development, Drug Efficacy and Safety Profiles , 2010 .

[15]  R. Dietz,et al.  Exposure and effects assessment of persistent organohalogen contaminants in arctic wildlife and fish. , 2010, The Science of the total environment.

[16]  Joshua F. Robinson,et al.  A systems-based approach to investigate dose- and time-dependent methylmercury-induced gene expression response in C57BL/6 mouse embryos undergoing neurulation. , 2010, Birth defects research. Part B, Developmental and reproductive toxicology.

[17]  G. Schieven,et al.  Rapid Activation of Glutamate Cysteine Ligase following Oxidative Stress* , 2010, The Journal of Biological Chemistry.

[18]  B. Mannervik,et al.  Substrate specificity combined with stereopromiscuity in glutathione transferase A4-4-dependent metabolism of 4-hydroxynonenal. , 2010, Biochemistry.

[19]  C. Sonne Health effects from long-range transported contaminants in Arctic top predators: An integrated review based on studies of polar bears and relevant model species. , 2010, Environment international.

[20]  L. D. de Groot,et al.  Fish-oil supplementation induces antiinflammatory gene expression profiles in human blood mononuclear cells. , 2009, The American journal of clinical nutrition.

[21]  L. Fried,et al.  Glutathione peroxidase enzyme activity in aging. , 2008, The journals of gerontology. Series A, Biological sciences and medical sciences.

[22]  R. Dietz,et al.  Comparative fate of organohalogen contaminants in two top carnivores in Greenland: captive sledge dogs and wild polar bears. , 2008, Comparative biochemistry and physiology. Toxicology & pharmacology : CBP.

[23]  T. O'hara,et al.  Effects of climate change on Arctic marine mammal health. , 2008, Ecological applications : a publication of the Ecological Society of America.

[24]  P. Bowers,et al.  Hair analysis in sled dogs (Canis lupus familiaris) illustrates a linkage of mercury exposure along the Yukon River with human subsistence food systems. , 2007, The Science of the total environment.

[25]  Shyam Biswal,et al.  Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. , 2007, Annual review of pharmacology and toxicology.

[26]  G. Bossard Marine Mammals as Sentinel Species for Oceans and Human Health , 2006 .

[27]  Ash A. Alizadeh,et al.  Cell-type specific gene expression profiles of leukocytes in human peripheral blood , 2006, BMC Genomics.

[28]  D. Muir,et al.  Spatial and temporal trends of contaminants in terrestrial biota from the Canadian Arctic. , 2005, The Science of the total environment.

[29]  J. Raser,et al.  Noise in Gene Expression: Origins, Consequences, and Control , 2005, Science.

[30]  M. M. Krahn,et al.  Determining aromatic hydrocarbons and chlorinated hydrocarbons in sediments and tissues using accelerated solvent extraction and gas chromatography/mass spectrometry , 2005 .

[31]  Jean YH Yang,et al.  Bioconductor: open software development for computational biology and bioinformatics , 2004, Genome Biology.

[32]  Y. Kuroda,et al.  Polychlorinated Biphenyls Suppress Thyroid Hormone Receptor-mediated Transcription through a Novel Mechanism* , 2004, Journal of Biological Chemistry.

[33]  N. Englert Fine particles and human health--a review of epidemiological studies. , 2004, Toxicology letters.

[34]  D. Ritter,et al.  Oral Vaccination of Captive Arctic Foxes with Lyophilized SAG2 Rabies Vaccine , 2004, Journal of wildlife diseases.

[35]  H. Tamura,et al.  Oxidative stress induces GSTP1 and CYP3A4 expression in the human erythroleukemia cell line, K562. , 2004, Biological & pharmaceutical bulletin.

[36]  T. O'hara,et al.  Organochlorine contaminant and stable isotope profiles in Arctic fox (Alopex lagopus) from the Alaskan and Canadian Arctic. , 2003, Environmental pollution.

[37]  Ash A. Alizadeh,et al.  Individuality and variation in gene expression patterns in human blood , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[38]  M. Yılmaz,et al.  Increased oxidative stress and hypozincemia in male obesity. , 2002, Clinical biochemistry.

[39]  Steffen Loft,et al.  Personal PM2.5 exposure and markers of oxidative stress in blood. , 2002, Environmental health perspectives.

[40]  Ken Itoh,et al.  Transcription Factor Nrf2 Coordinately Regulates a Group of Oxidative Stress-inducible Genes in Macrophages* , 2000, The Journal of Biological Chemistry.

[41]  C. Kunsch,et al.  Oxidative stress as a regulator of gene expression in the vasculature. , 1999, Circulation research.

[42]  R. Stephenson,et al.  Annual, seasonal, and habitat-related variation in feeding habits of the arctic fox (Alopex lagopus) on St. Lawrence Island, Bering Sea , 1989 .

[43]  A. L. Jensen,et al.  Alterations in thyroid hormone status in Greenland sledge dogs exposed to whale blubber contaminated with organohalogen compounds. , 2011, Ecotoxicology and environmental safety.

[44]  N. Mölders,et al.  Investigations on meteorological conditions for elevated PM2.5 in Fairbanks, Alaska , 2011 .

[45]  R. Dietz,et al.  Mineral density and biomechanical properties of bone tissue from male Arctic foxes (Vulpes lagopus) exposed to organochlorine contaminants and emaciation. , 2009, Comparative biochemistry and physiology. Toxicology & pharmacology : CBP.

[46]  R. Dietz,et al.  Dietary, age and trans-generational effects on the fate of organohalogen contaminants in captive sledge dogs in Greenland. , 2009, Environment international.

[47]  Terence P. Speed,et al.  Quality Assessment of Affymetrix GeneChip Data , 2005 .

[48]  C. Kapel Diet of Arctic Foxes (Alopex lagopus) in Greenland , 1999 .

[49]  H. Greim,et al.  [Polychlorated biphenyls and cytochrome P-450]. , 1974, Verhandlungen der Deutschen Gesellschaft fur Innere Medizin.