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
  • 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
  • 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
  • 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
  • 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
  • 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, 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
  • 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
  • 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