Adverse outcome pathway-based comparison of multiple mechanisms of action of bitumen-derived polycyclic aromatic hydrocarbons mixtures using transcriptomic dose-response modeling and the transgenic rodent mutation assay

Funding period: 2020-2024
Lead: Jason O'Brien
Total GRDI funding: $180,000

This research investigates how the genomes of wildlife populations are impacted by chemical and non-chemical environmental stressors. Target populations include river otter and mink that are exposed to polycyclic aromatic hydrocarbons in the oil sands area, and boreal caribou that are threatened by climate change and habitat loss. Using a combination of experimental exposures, wild samples and existing genomics data sets, we will measure various markers of genome stability (somatic and germline microsatellite and single nucleotide mutations) to determine how environmental stressors impact genome health in these populations.

Publications
  • Beal MA, Meier MJ, LeBlanc DP, Maurice C, O'Brien JM, Yauk CL, Marchetti F. 2020. Chemically induced mutations in a MutaMouse reporter gene inform mechanisms underlying human cancer mutational signatures. Commun. Biol. 3(1):438. https://doi.org/10.1038/s42003-020-01174-y
  • Chauhan V, Wilkins RC, Beaton D, Sachana M, Delrue N, Yauk C, O'Brien J, Marchetti F, Halappanavar S, Boyd M, Villeneuve D, Barton-Maclaren TS, Meek B, Anghel C, Heghes C, Barber C, Perkins E, Leblanc J, Burtt J, Laakso H, Laurier D, Lazo T, Whelan M, Thomas R, Cool D. 2021. Bringing together scientific disciplines for collaborative undertakings: a vision for advancing the adverse outcome pathway framework. Int. J Radiat. Biol. 97(4):431-441. https://doi.org/10.1080/09553002.2021.1884314
  • Crump D, Sharin T, Chiu S, O'Brien JM. 2021. In Vitro Screening of 21 Bisphenol A Replacement Alternatives: Compared with Bisphenol A, the Majority of Alternatives Are More Cytotoxic and Dysregulate More Genes in Avian Hepatocytes. Environ Toxicol Chem. 2021 Jul;40(7):2026-2033. https://doi.org/10.1002/etc.5032
  • Douglas GR, Beevers C, Gollapudi B, Keig-Shevlin Z, Kirkland D, O'Brien JM, van Benthem J, Yauk CL, Young RR, Marchetti F. 2022. Impact of sampling time on the detection of mutations in rapidly proliferating tissues using transgenic rodent gene mutation models: A review. Environ Mol Mutagen. 63(8-9):376-388. https://doi.org/10.1002/em.22514
  • Gyasi H, Curry J, Browning J, Ha K, Thomas PJ, O'Brien JM. 2022. Microsatellite mutation frequencies in river otters (Lontra Canadensis) from the Athabasca Oil Sands region are correlated to polycyclic aromatic compound tissue burden. Environ. Mol. Mutagen. 63(4):172-183. https://doi.org/10.1002/em.22482
  • Ha K, Xia P, Crump D, Saini A, Harner T, O'Brien J. 2021. Cytotoxic and Transcriptomic Effects in Avian Hepatocytes Exposed to a Complex Mixture from Air Samples, and Their Relation to the Organic Flame Retardant Signature. Toxics. 30;9(12):324. https://doi.org/10.3390/toxics9120324
  • Harrill JA, Viant MR, Yauk CL, Sachana M, Gant TW, Auerbach SS, Beger RD, Bouhifd M, O'Brien J, Burgoon L, Caiment F, Carpi D, Chen T, Chorley BN, Colbourne J, Corvi R, Debrauwer L, O'Donovan C, Ebbels TMD, Ekman DR, Faulhammer F, Gribaldo L, Hilton GM, Jones SP, Kende A, Lawson TN, Leite SB, Leonards PEG, Luijten M, Martin A, Moussa L, Rudaz S, Schmitz O, Sobanski T, Strauss V, Vaccari M, Vijay V, Weber RJM, Williams AJ, Williams A, Thomas RS, Whelan M. 2021. Progress towards an OECD reporting framework for transcriptomics and metabolomics in regulatory toxicology. Regul. Toxicol. Pharmacol. 125:105020. https://doi.org/10.1016/j.yrtph.2021.105020
  • Huliganga E, Marchetti F, O'Brien JM, Chauhan V, Yauk CL. 2022. A case study on integrating a new key event into an existing adverse outcome pathway on oxidative DNA damage: challenges and approaches in a data-rich area. Front. Toxicol. 4:827328. https://doi.org/10.3389/ftox.2022.827328
  • Johnson KJ, Auerbach SS, Stevens T, Barton-Maclaren TS, Costa E, Currie RA, Dalmas Wilk D, Haq S, Rager JE, Reardon AJF, Wehmas L, Williams A, O'Brien J, Yauk C, LaRocca JL, Pettit SA. 2022. Transformative Vision for an Omics-Based Regulatory Chemical Testing Paradigm. Toxicol Sci. 190(2):127-132. https://doi.org/10.1093/toxsci/kfac097
  • Morris AD, Braune BM, Gamberg M, Stow J, O'Brien J, Letcher RJ. 2022. Temporal change and the influence of climate and weather factors on mercury concentrations in Hudson Bay polar bears, caribou, and seabird eggs. Environ. Res. 207:112169. https://doi.org/10.1016/j.envres.2021.112169
  • Nguyen PTT, Pagé-Larivière F, Williams K, O'Brien J, Crump D. 2022. Developmental and Hepatic Gene Expression Changes in Chicken Embryos Exposed to p-Tert-Butylphenyl Diphenyl Phosphate and Isopropylphenyl Phosphate via Egg Injection. Environ Toxicol Chem. 41(3):739-747. https://doi.org/10.1002/etc.5274
  • O'Brien JM, Yauk CL. 2022. Introducing AOP Reports: Collaborative review and publication of adverse outcome pathways. Environ Mol Mutagen. 63(3):116-117. https://doi.org/10.1002/em.22481
  • Svingen T, Villeneuve DL, Knapen D, Panagiotou EM, Draskau MK, Damdimopoulou P, O'Brien JM. 2021. A Pragmatic Approach to Adverse Outcome Pathway Development and Evaluation. Toxicol. Sci. 184(2):183-190. https://doi.org/10.1093/toxsci/kfab113
  • Provencher JF, Thomas PJ, Pauli B, Braune BM, Franckowiak RP, Gendron M, Savard G, Sarma SN, Crump D, Zahaby Y, O'Brien J, Mallory ML. 2020. Polycyclic aromatic compounds (PACs) and trace elements in four marine bird species from northern Canada in a region of natural marine oil and gas seeps. Sci. Total. Environ. 744:140959. https://doi.org/10.1016/j.scitotenv.2020.140959
  • Sarma SN, Thomas PJ, Naz S, Pauli B, Crump D, Zahaby Y, O'Brien JM, Mallory ML, Franckowiak RP, Gendron M, Provencher JF. 2022. Metabolomic profiles in relation to benchmark polycyclic aromatic compounds (PACs) and trace elements in two seabird species from Arctic Canada. Environ Res. 204(Pt B):112022. https://doi.org/10.1016/j.envres.2021.112022
  • Sharin T, Crump D, O'Brien JM. 2020. Evaluation of the Aryl Hydrocarbon Receptor Response in LMH 3D Spheroids. Environ. Toxicol. Chem. 39(9):1693-1701. https://doi.org/10.1002/etc.4783
  • Sharin T, Crump D, O'Brien JM. 2022. Toxicity screening of bisphenol A replacement compounds: cytotoxicity and mRNA expression in LMH 3D spheroids. Environ Sci Pollut Res Int. 29(29):44769-44778. https://doi.org/10.1007/s11356-022-18812-z
  • Sharin T, Gyasi H, Jones SP, Crump D, O'Brien JM. 2021. Concentration- and time-dependent induction of Cyp1a and DNA damage response by benzo(a)pyrene in LMH three-dimensional spheroids. Environ. Mol. Mutagen. 62(5):319-327. https://doi.org/10.1002/em.22433
  • Sharin T, Williams KL, Chiu S, Crump D, O'Brien JM. 2021. Toxicity Screening of Bisphenol A Replacement Compounds: Cytotoxicity and mRNA Expression in Primary Hepatocytes of Chicken and Double-Crested Cormorant. Environ Toxicol Chem. 40(5):1368-1378. https://doi.org/10.1002/etc.4985
  • Sharin T, Gyasi H, Williams KL, Crump D, O'Brien JM. 2021. Effects of two Bisphenol A replacement compounds, 1,7-bis (4-hydroxyphenylthio)-3,5-dioxaheptane and Bisphenol AF, on development and mRNA expression in chicken embryos. Ecotoxicol Environ Saf. 215:112140. https://doi.org/10.1016/j.ecoenv.2021.112140
  • Sobanski T, Strauss V, Vaccari M, Vijay V, Weber RJM, Williams AJ, Williams A, Thomas RS, Whelan M. 2021. Progress towards an OECD reporting framework for transcriptomics and metabolomics in regulatory toxicology. Regul. Toxicol. Pharmacol. 125:105020. https://doi.org/10.1016/j.yrtph.2021.105020
  • Svingen T, Villeneuve DL, Knapen D, Panagiotou EM, Draskau MK, Damdimopoulou P, O'Brien JM. 2021. A Pragmatic Approach to Adverse Outcome Pathway Development and Evaluation. Toxicol. Sci. 184(2):183-190. https://doi.org/10.1093/toxsci/kfab113
  • Tanabe S, O'Brien J, Tollefsen KE, Kim Y, Chauhan V, Yauk C, Huliganga E, Rudel RA, Kay JE, Helm JS, Beaton D, Filipovska J, Sovadinova I, Garcia-Reyero N, Mally A, Poulsen SS, Delrue N, Fritsche E, Luettich K, La Rocca C, Yepiskoposyan H, Klose J, Danielsen PH, Esterhuizen M, Jacobsen NR, Vogel U, Gant TW, Choi I, FitzGerald R. 2022. Reactive Oxygen Species in the Adverse Outcome Pathway Framework: Toward Creation of Harmonized Consensus Key Events. Front Toxicol. 4:887135. https://doi.org/10.3389/ftox.2022.887135
  • Xia P, Crump D, Chiu S, Chan HM, O'Brien JM. 2020. Toxicogenomic Assessment of Complex Chemical Signatures in Double-Crested Cormorant Embryos from Variably Contaminated Great Lakes Sites. Environ Sci Technol. 16;54(12):7504-7512. https://doi.org/10.1021/acs.est.0c02725
  • Xia P, Peng Y, Fang W, Tian M, Shen Y, Ma C, Crump D, O'Brien JM, Shi W, Zhang X. 2021. Cross-Model Comparison of Transcriptomic Dose-Response of Short-Chain Chlorinated Paraffins. Environ. Sci. Technol. 15;55(12):8149-8158. https://doi.org/10.1021/acs.est.1c00975
  • Zahaby Y, Xia P, Crump D, Provencher JF, Thomas PJ, Pauli B, Braune BM, Franckowiak RP, Gendron M, Savard G, Sarma SN, Mallory ML, O'Brien J. 2021. ToxChip PCR Arrays for Two Arctic-Breeding Seabirds: Applications for Regional Environmental Assessments. Environ. Sci. Technol. 55(11):7521-7530. https://doi.org/10.1021/acs.est.1c00229

Contact us

For additional information, please contact:
Genomics R&D Initiative
Email: info@grdi-irdg.collaboration.gc.ca

From: Genomics R&D Initiative

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