Superfund Research Program

Elucidating Metabolic and Physicochemical Mechanisms of PAH Susceptibility in Toxicity Test Systems and Humans

Project Leader: Jordan N. Smith (Pacific Northwest National Laboratory)
Grant Number: P42ES016465
Funding Period: 2009-2025

Project-Specific Links

Publications

2024

• Gaither KA, Garcia WL, Tyrrell KJ, Wright AT, Smith JN. 2024. Activity-based protein profiling to probe relationships between cytochrome P450 enzymes and early-age metabolism of two polycyclic aromatic hydrocarbons (PAHs): Phenanthrene and retene. Chem Res Toxicol doi:10.1021/acs.chemrestox.3c00424
• Rude CI, Wilson LB, La Du JK, Lalli P, Colby S, Schultz K, Smith JN, Waters KM, Tanguay RL. 2024. Aryl hydrocarbon receptor-dependent toxicity by retene requires metabolic competence. Toxicol Sci doi:10.1093/toxsci/kfae098 PMID:39107868

2023

• Maier ML, Siddens LK, Pennington JM, Uesugi S, Tilton SC, Vertel EA, Anderson KA, Tidwell LG, Ognibene T, Turteltaub KW, Smith JN, Williams DE. 2023. Benzo[a]pyrene toxicokinetics in humans following dietary supplementation with 3,3'-diindolylmethane (DIM) or brussels sprouts. Toxicol Appl Pharmacol 460:116377. doi:10.1016/j.taap.2023.116377 PMID:36642108 PMCID:PMC9946811
• Vermillion Maier ML, Siddens LK, Pennington J, Uesugi S, Labut EM, Vertel EA, Anderson KA, Tidwell LG, Tilton SC, Ognibene T, Turteltaub KW, Smith JN, Williams DE. 2023. Impact of phenanthrene co-administration on the toxicokinetics of benzo[a]pyrene in humans. UPLC-accelerator mass spectrometry following oral microdosing. Chem Biol Interact 382:110608. doi:10.1016/j.cbi.2023.110608

2022

• Garcia WL, Miller CJ, Lomas GX, Gaither KA, Tyrrell KJ, Smith JN, Brandvold KR, Wright AT. 2022. Profiling how the gut microbiome modulates host xenobiotic metabolism in response to benzo[a]pyrene and 1-nitropyrene exposure. Chem Res Toxicol 35(4):585-596. doi:10.1021/acs.chemrestox.1c00360
• Pande P, Madeen E, Williams DE, Crowell SR, Ognibene T, Turteltaub KW, Corley RA, Smith JN. 2022. Translating dosimetry of Dibenzo[def,p]chrysene (DBC) and metabolites across dose and species using physiologically based pharmacokinetic (PBPK) modeling. Toxicol Appl Pharmacol 438:doi:10.1016/j.taap.2021.115830 PMID:34933053 PMCID:PMC9264404
• Smith JN, Gaither KA, Pande P. 2022. Competitive metabolism of polycyclic aromatic hydrocarbons (PAHs): An assessment using in vitro metabolism and physiologically based pharmacokinetic (PBPK) modeling. Int J Environ Res Public Health 19(14):8266. doi:10.3390/ijerph19148266 PMID:35886113 PMCID:PMC9323266
• Vermillion Maier ML, Siddens LK, Pennington JM, Uesugi S, Anderson KA, Tidwell LG, Tilton SC, Ognibene T, Turteltaub KW, Smith JN, Williams DE. 2022. Benzo a pyrene (BaP) metabolites predominant in human plasma following escalating oral micro-dosing with C-14 -BaP. Environ Int 159:doi:10.1016/j.envint.2021.107045 PMID:34920278 PMCID:PMC8791557

2021

• Stoddard EG, Nag S, Martin J, Tyrrell KJ, Gibbins T, Anderson KA, Shukla AK, Corley RA, Wright AT, Smith JN. 2021. Exposure to an environmental mixture of polycyclic aromatic hydrocarbons induces hepatic cytochrome P450 enzymes in mice. Chem Res Toxicol 34(9):2145-2156. doi:10.1021/acs.chemrestox.1c00235 PMID:34472326

2019

• Madeen E, Siddens LK, Uesugi S, McQuistan TJ, Corley RA, Smith JN, Waters KM, Tilton SC, Anderson KA, Ognibene T, Turteltaub KW, Williams DE. 2019. Toxicokinetics of benzo[a]pyrene in humans: Extensive metabolism as determined by UPLC-accelerator mass spectrometry following oral micro-dosing. Toxicol Appl Pharmacol 364:97-105. doi:10.1016/j.taap.2018.12.010 PMID:30582946 PMCID:PMC6369707
• Stoddard EG, Nag S, Martin J, Killinger BJ, Corley RA, Smith JN, Wright AT. 2019. Benzo[a]pyrene induction of glutathione S-transferases: an activity-based protein profiling investigation. Chem Res Toxicol 32(6):1259-1267. doi:10.1021/acs.chemrestox.9b00069 PMID:30938511
• Thomas DG, Shankaran H, Truong L, Tanguay RL, Waters KM. 2019. Time-dependent behavioral data from zebrafish reveals novel signatures of chemical toxicity using point of departure analysis. Comput Toxicol 9:50-60. doi:10.1016/j.comtox.2018.11.001 PMID:31485548 PMCID:PMC6726397

2018

• Hummel JM, Madeen E, Siddens LK, Uesugi S, McQuistan TJ, Anderson KA, Turteltaub KW, Ognibene T, Bench G, Krueger SK, Harris S, Smith JN, Tilton SC, Baird WM, Williams DE. 2018. Pharmacokinetics of [(14)C]-Benzo[a]pyrene (BaP) in humans: Impact of Co-Administration of smoked salmon and BaP dietary restriction. Food Chem Toxicol 115:136-147. doi:10.1016/j.fct.2018.03.003 PMID:29518434 PMCID:PMC5935529
• Sadler NC, Webb-Robertson B, Clauss TR, Pounds J, Corley RA, Wright AT. 2018. High-fat diets alter the modulatory efects of xenobiotics on cytochrome P450 activities. Chem Res Toxicol 31:308-318. doi:10.1021/acs.chemrestox.8b00008 PMID:29688711
• Stoddard EG, Volk RF, Carson JP, Ljungberg CM, Murphree TA, Smith JN, Sadler NC, Shukla AK, Ansong C, Wright AT. 2018. Multifunctional activity-based protein profiling of the developing lung. J Proteome Res 17:2623-2634. doi:10.1021/acs.jproteome.8b00086 PMID:29972024

2017

• Shrivastava M, Lou S, Zelenyuk A, Easter RC, Corley RA, Thrall BD, Rasch PJ, Fast JD, Simonich SL, Shen H, Tao S. 2017. Global long-range transport and lung cancer risk from polycyclic aromatic hydrocarbons shielded by coatings of organic aerosol. Proc Natl Acad Sci U S A 114(6):1246-1251. doi:10.1073/pnas.1618475114 PMID:28115713 PMCID:PMC5307436
• Smith JN, Mehinagic D, Nag S, Crowell SR, Corley RA. 2017. In vitro metabolism of benzo[a]pyrene-7,8-dihydrodiol and dibenzo[def,p]chrysene-11,12 diol in rodent and human hepatic microsomes. Toxicol Lett 269:23-32. doi:10.1016/j.toxlet.2017.01.008 PMID:28119020
• Stoddard EG, Killinger BJ, Nair RN, Sadler NC, Volk RF, Purvine SO, Shukla AK, Smith JN, Wright AT. 2017. Activity-based probes for Isoenzyme- and site-specific functional characterization of Glutathione S-Transferases. J Am Chem Soc 139(45):16032-16035. doi:10.1021/jacs.7b07378 PMID:29068682

2016

• Sadler NC, Nandhikonda P, Webb-Robertson B, Ansong C, Anderson LN, Smith JN, Corley RA, Wright AT. 2016. Hepatic cytochrome P450 activity, abundance, and expression throughout human development. Drug Metab Dispos 44(7):984-991. doi:10.1124/dmd.115.068593 PMID:27084891 PMCID:PMC4931891
• Teeguarden J, Tan Y, Edwards SW, Leonard JA, Anderson KA, Corley RA, Kile ML, Simonich SL, Stone D, Tanguay RL, Waters KM, Harper SL, Williams DE. 2016. Completing the link between exposure science and toxicology for improved environmental health decision making: the aggregate exposure pathway framework. Environ Sci Technol 50(9):4579-4586. doi:10.1021/acs.est.5b05311 PMID:26759916 PMCID:PMC4854780

2015

• Madeen E, Corley RA, Crowell SR, Turteltaub KW, Ognibene T, Malfatti MA, McQuistan TJ, Garrard M, Sudakin D, Williams DE. 2015. Human in vivo pharmacokinetics of [(14)C]dibenzo[def,p]chrysene by accelerator mass spectrometry following oral microdosing. Chem Res Toxicol 28(1):126-134. doi:10.1021/tx5003996 PMID:25418912 PMCID:PMC4303324

2013

• Crowell SR, Sharma AK, Amin S, Soelberg JJ, Sadler NC, Wright AT, Baird WM, Williams DE, Corley RA. 2013. Impact of pregnancy on the pharmacokinetics of dibenzo[def,p]chrysene in mice. Toxicol Sci 135(1):48-62. doi:10.1093/toxsci/kft124 PMID:23744095 PMCID:PMC3748759

2012

• Shorey LE, Castro DJ, Baird WM, Siddens LK, Lohr CV, Matzke MM, Waters KM, Corley RA, Williams DE. 2012. Transplacental carcinogenesis with dibenzo[def,p]chrysene (DBC): Timing of maternal exposures determines target tissue response in offspring. Cancer Lett 317(1):49-55. doi:10.1016/j.canlet.2011.11.010 PMID:22085489 PMCID:PMC3269513

2011

• Crowell SR, Amin S, Anderson KA, Krishnegowda G, Sharma AK, Soelberg JJ, Williams DE, Corley RA. 2011. Preliminary physiologically based pharmacokinetic models for benzo a pyrene and dibenzo def,p chrysene in rodents. Toxicol Appl Pharmacol 257:365-376. doi:10.1016/j.taap.2011.09.020 PMID:22001385 PMCID:PMC3226888