Semi-volatile PCBs: Sources, Exposures, Toxicities

Summary

Principal Investigator: Larry W Robertson
Abstract: Airborne PCBs are those that have higher vapor pressures, lower chlorination, and are substrates for metabolic activation. We hypothesize that lower chlorinated airborne PCBs and their natural electrophilic metabolites interact with DNA and DNA-associated proteins and/or initiate oxidative events that alter the intracellular redox environment, thereby compromising cellular structures and functions. Our data show that PCBs are initiators in rat liver and that PCB3 (4-chlorobiphenyl) induces mutations in the liver and possibly lung of transgenic BigBlue rats after ip injection. Also, PCB3 metabolites cause various, compound-specific types of genotoxic damage in cells in culture. We have shown that prostaglandin synthase and myeloperoxidase bioactivate dihydroxy-PCBs and that the PCB-quinones can react with nucleophiles like GSH by Michael addition or a substitution reaction with dechlorination. We have also observed, for the first time, a PCB semiquinone radical in cells. We therefore propose to extend our studies to: 1) Examine the mechanisms of PCB genotoxicity by comparing nuclear vs. mitochondrial effects and elucidating PCB interactions with DNA-associated protein;2) Investigate interactions of airborne PCBs and their metabolites with telomeres and telomerase;3) Determine the reactions of PCB-semiquinone radicals and how factors, such as conjugation with thiols, affect this reactivity;4) Analyze the genotoxicity of airborne PCBs after inhalation exposure and explore mechanisms to ameliorate/mediate against those effects. Jointly these studies may explain which and how PCBs are genotoxic, which organs, subcellular structures, and macromolecules are the targets, the mechanisms of these reactions, and whether these upset the delicate redox balance of the natural environment of the cell. Emphasis is placed on the kinetics and consequences of inhalation exposure to airborne PCBs. These data and dietary studies in the last Aim will provide a scientific basis for risk assessment and advice for stakeholders with the ultimate goal to protect highly-exposed individuals and populations.
Funding Period: 2005-04-01 - 2015-03-31
more information: NIH RePORT

Top Publications

  1. pmc Biological and tumor-promoting effects of dioxin-like and non-dioxin-like polychlorinated biphenyls in mouse liver after single or combined treatment
    Benjamin Rignall
    Department of Toxicology, University of Tubingen, 72074 Tuebingen, Germany
    Toxicol Sci 133:29-41. 2013
  2. pmc Subchronic inhalation exposure study of an airborne polychlorinated biphenyl mixture resembling the Chicago ambient air congener profile
    Xin Hu
    Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, Iowa 52242, United States
    Environ Sci Technol 46:9653-62. 2012
  3. pmc Disruption of phosphatidylcholine monolayers and bilayers by perfluorobutane sulfonate
    E Davis Oldham
    Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, Iowa 52242, USA
    J Phys Chem B 116:9999-10007. 2012
  4. pmc N-acetylcysteine (NAC) diminishes the severity of PCB 126-induced fatty liver in male rodents
    Ian K Lai
    Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, IA, United States
    Toxicology 302:25-33. 2012
  5. pmc Manganese superoxide dismutase regulates a metabolic switch during the mammalian cell cycle
    Ehab H Sarsour
    Free Radical and Radiation Biology Division, Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242, USA
    Cancer Res 72:3807-16. 2012
  6. pmc Regulation of paraoxonase 1 (PON1) in PCB 126-exposed male Sprague Dawley rats
    Hua Shen
    Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, 100 Oakdale Campus, IREH, Iowa City, IA, USA
    Toxicol Lett 209:291-8. 2012
  7. pmc Density functional theory study of semiquinone radical anions of polychlorinated biphenyls in the syn- and anti-like conformation
    Jyothirmai Ambati
    Department of Chemical and Materials Engineering, University of Kentucky, Lexington, Kentucky 40506 0046, United States
    J Phys Chem A 116:1586-95. 2012
  8. pmc Spatial distribution of chlordanes and PCB congeners in soil in Cedar Rapids, Iowa, USA
    Andres Martinez
    Department of Civil and Environmental Engineering, IIHR Hydroscience and Engineering, The University of Iowa, 4105 SC, Iowa City, IA 52242, USA
    Environ Pollut 161:222-8. 2012
  9. pmc PCB153 reduces telomerase activity and telomere length in immortalized human skin keratinocytes (HaCaT) but not in human foreskin keratinocytes (NFK)
    P K Senthilkumar
    Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA 52242 5000, USA
    Toxicol Appl Pharmacol 259:115-23. 2012
  10. pmc Role of oil vehicle on hepatic cell proliferation in PCB-treated rats
    Rodica Petruta Bunaciu
    Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40506 0054, USA
    J Environ Pathol Toxicol Oncol 30:273-82. 2011

Research Grants

  1. EPIDEMIOLOGY OF ALCOHOL PROBLEMS
    Thomas K Greenfield; Fiscal Year: 2013
  2. Elucidating Risks: From Exposure and Mechanism to Outcome
    James A Swenberg; Fiscal Year: 2013

Detail Information

Publications177 found, 100 shown here

  1. pmc Biological and tumor-promoting effects of dioxin-like and non-dioxin-like polychlorinated biphenyls in mouse liver after single or combined treatment
    Benjamin Rignall
    Department of Toxicology, University of Tubingen, 72074 Tuebingen, Germany
    Toxicol Sci 133:29-41. 2013
    ..These results suggest weak but significant response-additive effects of the 2 PCBs when given in combination. They also suggest that the Cyp biomarkers tend to overestimate the carcinogenic response produced by the PCBs in mouse liver...
  2. pmc Subchronic inhalation exposure study of an airborne polychlorinated biphenyl mixture resembling the Chicago ambient air congener profile
    Xin Hu
    Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, Iowa 52242, United States
    Environ Sci Technol 46:9653-62. 2012
    ....
  3. pmc Disruption of phosphatidylcholine monolayers and bilayers by perfluorobutane sulfonate
    E Davis Oldham
    Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, Iowa 52242, USA
    J Phys Chem B 116:9999-10007. 2012
    ..In summary, PFBS disrupted different model lipid assemblies, indicating potential for PFBS to be a human toxicant. However, the effects of PFBS are not as pronounced as those seen with longer chain PFAAs...
  4. pmc N-acetylcysteine (NAC) diminishes the severity of PCB 126-induced fatty liver in male rodents
    Ian K Lai
    Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, IA, United States
    Toxicology 302:25-33. 2012
    ..The mechanism of this protective effect appears to be independent of NAC as a source of cysteine/precursor of glutathione...
  5. pmc Manganese superoxide dismutase regulates a metabolic switch during the mammalian cell cycle
    Ehab H Sarsour
    Free Radical and Radiation Biology Division, Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242, USA
    Cancer Res 72:3807-16. 2012
    ..These results support the hypothesis that MnSOD regulates a "metabolic switch" during progression from quiescent through the proliferative cycle. We propose MnSOD as a new molecular player contributing to the Warburg effect...
  6. pmc Regulation of paraoxonase 1 (PON1) in PCB 126-exposed male Sprague Dawley rats
    Hua Shen
    Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, 100 Oakdale Campus, IREH, Iowa City, IA, USA
    Toxicol Lett 209:291-8. 2012
    ....
  7. pmc Density functional theory study of semiquinone radical anions of polychlorinated biphenyls in the syn- and anti-like conformation
    Jyothirmai Ambati
    Department of Chemical and Materials Engineering, University of Kentucky, Lexington, Kentucky 40506 0046, United States
    J Phys Chem A 116:1586-95. 2012
    ..These findings suggest that SQs(•-) in both the syn- and antilike conformation may interact differently with target molecules, which may have implications for the toxicity of PCBs...
  8. pmc Spatial distribution of chlordanes and PCB congeners in soil in Cedar Rapids, Iowa, USA
    Andres Martinez
    Department of Civil and Environmental Engineering, IIHR Hydroscience and Engineering, The University of Iowa, 4105 SC, Iowa City, IA 52242, USA
    Environ Pollut 161:222-8. 2012
    ....
  9. pmc PCB153 reduces telomerase activity and telomere length in immortalized human skin keratinocytes (HaCaT) but not in human foreskin keratinocytes (NFK)
    P K Senthilkumar
    Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA 52242 5000, USA
    Toxicol Appl Pharmacol 259:115-23. 2012
    ....
  10. pmc Role of oil vehicle on hepatic cell proliferation in PCB-treated rats
    Rodica Petruta Bunaciu
    Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40506 0054, USA
    J Environ Pathol Toxicol Oncol 30:273-82. 2011
    ..These studies show that the oil vehicle is important in cell proliferation after PCB exposure, with MCT oil appearing to be protective...
  11. pmc Biodegradation of mono-hydroxylated PCBs by Burkholderia xenovorans
    Rouzbeh Tehrani
    Department of Civil and Environmental Engineering, Temple University, Philadelphia, PA 19122, USA
    Biotechnol Lett 34:2247-52. 2012
    ..These results provide the first evidence that bacteria are able to metabolize PCB derivatives hydroxylated on the non-chlorinated ring...
  12. pmc 2,2',3,5',6-Pentachlorobiphenyl (PCB 95) and its hydroxylated metabolites are enantiomerically enriched in female mice
    Izabela Kania-Korwel
    Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, Iowa, USA
    Environ Sci Technol 46:11393-401. 2012
    ....
  13. pmc PCBs and OH-PCBs in serum from children and mothers in urban and rural U.S. communities
    Rachel F Marek
    Department of Civil and Environmental Engineering, The University of Iowa, Iowa City, Iowa 52242, United States
    Environ Sci Technol 47:3353-61. 2013
    ..This is the first temporally and methodologically consistent study to evaluate all 209 PCBs and major metabolites in two generations of people living in urban and rural areas of the United States...
  14. pmc Modification of the catalytic function of human hydroxysteroid sulfotransferase hSULT2A1 by formation of disulfide bonds
    Xiaoyan Qin
    Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, Iowa, USA
    Drug Metab Dispos 41:1094-103. 2013
    ..Thus, the formation of disulfide bonds in hSULT2A1 is a potentially important reversible mechanism for alterations in the rates of sulfation of both endogenous and xenobiotic substrates...
  15. pmc Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): results from a phase I clinical trial
    J L Welsh
    Department of Surgery, 1528 JCP UIHC, The University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
    Cancer Chemother Pharmacol 71:765-75. 2013
    ..A phase I clinical trial was performed to establish safety and tolerability of pharmacological ascorbate combined with gemcitabine in patients with biopsy-proven stage IV pancreatic adenocarcinoma...
  16. pmc Assigning atropisomer elution orders using atropisomerically enriched polychlorinated biphenyl fractions generated by microsomal metabolism
    Izabela Kania-Korwel
    Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, IA 52242, USA
    J Chromatogr A 1278:133-44. 2013
    ....
  17. pmc Inhibition of cytochromes P450 and the hydroxylation of 4-monochlorobiphenyl in whole poplar
    Guangshu Zhai
    Department of Civil and Environmental Engineering and IIHR Hydroscience and Engineering, The University of Iowa, Iowa City, Iowa 52242, United States
    Environ Sci Technol 47:6829-35. 2013
    ..A dose-response curve for each of the suicide inhibitors was developed. ..
  18. pmc Sulfate metabolites of 4-monochlorobiphenyl in whole poplar plants
    Guangshu Zhai
    Department of Civil and Environmental Engineering and IIHR Hydroscience and Engineering, The University of Iowa, Iowa City, Iowa 52242, United States
    Environ Sci Technol 47:557-62. 2013
    ..Results suggested that OH-PCB3s were the substrates of sulfotransferases which catalyzed the formation of PCB3 sulfates in the metabolic pathway of PCB3...
  19. ncbi Polychlorinated biphenyls (PCBs) as initiating agents in hepatocellular carcinoma
    Gabriele Ludewig
    The University of Iowa, 100 Oakdale Campus, IREH, Iowa City, IA 52242 5000, United States Electronic address
    Cancer Lett 334:46-55. 2013
    ..This review will provide an overview of our current knowledge of PCBs' genotoxic potential and mechanism of action, emphasizing the contributions of Dr. Ramesh Gupta during his tenures at the Universities of Kentucky and Louisville. ..
  20. pmc Inhibitors of hydroperoxide metabolism enhance ascorbate-induced cytotoxicity
    K E Olney
    Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242, USA
    Free Radic Res 47:154-63. 2013
    ..We conclude that inclusion of agents that inhibit cellular peroxide removal produced by pharmacological ascorbate leads to changes in the intracellular redox state resulting in enhanced cytotoxicity...
  21. pmc Identification of sulfated metabolites of 4-chlorobiphenyl (PCB3) in the serum and urine of male rats
    Kiran Dhakal
    Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, Iowa 52242, United States
    Chem Res Toxicol 25:2796-804. 2012
    ..18 ± 2.16 μg/mL. This is the first report that sulfated metabolites of PCBs are formed in vivo. These findings suggest a prospective approach for exposure assessment of LC-PCBs by analysis of phase II metabolites in urine...
  22. pmc 2,2',3,3',6,6'-Hexachlorobiphenyl (PCB 136) is enantioselectively oxidized to hydroxylated metabolites by rat liver microsomes
    Xianai Wu
    Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, Iowa 52242, USA
    Chem Res Toxicol 24:2249-57. 2011
    ....
  23. pmc Species difference in the regulation of cytochrome P450 2S1: lack of induction in rats by the aryl hydrocarbon receptor agonist PCB126
    Bingxuan Wang
    Human Toxicology, University of Iowa, Iowa City, USA
    Xenobiotica 41:1031-43. 2011
    ..PB and Dex had no effect on CYP2S1 mRNA levels. These observations show that in this model CYP2S1 is not, or only weakly, regulated by AhR and not induced by CAR or PXR activators...
  24. pmc Superoxide dismutase in redox biology: the roles of superoxide and hydrogen peroxide
    Garry R Buettner
    Free Radical and Radiation Biology, The University of Iowa, Iowa City, 52242 1181, USA
    Anticancer Agents Med Chem 11:341-6. 2011
    ..It is now realized that superoxide and hydrogen peroxide are essential for normal cellular and organism function. MnSOD appears to be a central player in the redox biology of cells and tissues...
  25. pmc Enantioselective biotransformation of chiral PCBs in whole poplar plants
    Guangshu Zhai
    Department of Civil and Environmental Engineering and IIHR Hydroscience and Engineering, The University of Iowa, Iowa City, Iowa 52242, United States
    Environ Sci Technol 45:2308-16. 2011
    ..This is the first evidence of enantioselectivity of chiral PCBs in whole plants, and suggests that poplars can enantioselectively biotransform at least one chiral PCB...
  26. pmc Aberrant promoter CpG methylation is a mechanism for impaired PHD3 expression in a diverse set of malignant cells
    Trenton L Place
    Molecular and Cellular Biology Program, The University of Iowa, Iowa City, Iowa, United States of America
    PLoS ONE 6:e14617. 2011
    ..This study explores the mechanism by which malignancies neither basally express PHD3 nor induce PHD3 under hypoxic conditions...
  27. pmc Substrate inhibition in human hydroxysteroid sulfotransferase SULT2A1: studies on the formation of catalytically non-productive enzyme complexes
    Hayrettin Ozan Gulcan
    Division of Medicinal and Natural Products Chemistry, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, USA
    Arch Biochem Biophys 507:232-40. 2011
    ..Our results indicate that hSULT2A1 forms non-productive ternary complexes that involve either DHEA or dehydroepiandrosterone sulfate, and the formation of these ternary complexes displays negative cooperativity in the binding of DHEA...
  28. pmc Physicochemical properties of hydroxylated polychlorinated biphenyls aid in predicting their interactions with rat sulfotransferase 1A1 (rSULT1A1)
    Yungang Liu
    University of Iowa, Iowa City, 52242 1112, United States
    Chem Biol Interact 189:153-60. 2011
    ....
  29. pmc Observation of an unusual electronically distorted semiquinone radical of PCB metabolites in the active site of prostaglandin H synthase-2
    Orarat Wangpradit
    Department of Occupational and Environmental Health, The University of Iowa, 100 Oakdale Campus, Iowa City, IA 52242 5000, USA
    Chemosphere 81:1501-8. 2010
    ..This study provides new insights into the formation of semiquinones from PCB metabolites and underscores the potential role of PGHS-2 in the metabolic activation of PCBs...
  30. pmc 3-Methylcholanthrene (3-MC) and 4-chlorobiphenyl (PCB3) genotoxicity is gender-related in Fischer 344 transgenic rats
    J A Jacobus
    Department of Occupational and Environmental Health, University of Iowa, 100 Oakdale Campus 124 IREH, Iowa City, IA 52242 5000, United States
    Environ Int 36:970-9. 2010
    ..Our analysis indicates that female transgenic BigBlue Fischer 344 rats are more resistant to PCB3 and 3-MC genotoxicity compared to their male counterparts...
  31. pmc Identification of hydroxylated metabolites of 3,3',4,4'-tetrachlorobiphenyl and metabolic pathway in whole poplar plants
    Guangshu Zhai
    Department of Civil and Environmental Engineering and IIHR Hydroscience and Engineering, The University of Iowa, Iowa City, IA 52242, USA
    Chemosphere 81:523-8. 2010
    ..However, the major mammalian metabolite, 4'OH-CB79 was not detected in any of the samples. The results suggest that the hydroxylated metabolic pathway of CB77 is via an epoxide intermediate in poplar...
  32. pmc Airborne polychlorinated biphenyls (PCBs) reduce telomerase activity and shorten telomere length in immortal human skin keratinocytes (HaCat)
    P K Senthilkumar
    Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, United States
    Toxicol Lett 204:64-70. 2011
    ..This significant inhibition of telomerase activity and reduction of telomere length by PCB congeners suggest a potential mechanism by which these compounds could lead to accelerated aging and cancer...
  33. pmc Oxidation of 3,4-dihydroxyphenylacetaldehyde, a toxic dopaminergic metabolite, to a semiquinone radical and an ortho-quinone
    David G Anderson
    Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242 1112, USA
    J Biol Chem 286:26978-86. 2011
    ..The involvement of this physiologically relevant enzyme in both oxidative stress and Parkinson disease underscores the potential importance of DOPAL in the pathogenesis of this condition...
  34. pmc Gas chromatographic analysis with chiral cyclodextrin phases reveals the enantioselective formation of hydroxylated polychlorinated biphenyls by rat liver microsomes
    Izabela Kania-Korwel
    Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, Iowa 52242, United States
    Environ Sci Technol 45:9590-6. 2011
    ..Overall, this study demonstrates for the first time that chiral PCBs, such as PCB 91, 95, 132, and 149, are enantioselectively metabolized to OH-PCBs by cytochrome P450 enzymes...
  35. pmc Structure-activity relationships for hydroxylated polychlorinated biphenyls as inhibitors of the sulfation of dehydroepiandrosterone catalyzed by human hydroxysteroid sulfotransferase SULT2A1
    Edugie J Ekuase
    Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, United States
    Chem Res Toxicol 24:1720-8. 2011
    ....
  36. pmc Record of PCB congeners, sorbents and potential toxicity in core samples in Indiana Harbor and Ship Canal
    Andres Martinez
    Department of Civil and Environmental Engineering, IIHR Hydroscience and Engineering, The University of Iowa, Iowa City, IA 52242, USA
    Chemosphere 85:542-7. 2011
    ..Both cores contain dioxin-like PCBs that are highest in concentration below the surface. The high levels of PCBs in the deep sediments are of concern because of plans to dredge this system...
  37. pmc Dietary selenium as a modulator of PCB 126-induced hepatotoxicity in male Sprague-Dawley rats
    Ian K Lai
    Interdisciplinary Graduate Program in Human Toxicology, College of Public Health, University of Iowa, Iowa City, Iowa 52242, USA
    Toxicol Sci 124:202-14. 2011
    ....
  38. pmc Crystal structure and density functional theory studies of toxic quinone metabolites of polychlorinated biphenyls
    Yang Song
    Key Laboratory on Luminescence and Real time Analysis, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chong Qing 400716, PR China
    Chemosphere 85:386-92. 2011
    ....
  39. pmc Preferential selection of MnSOD transcripts in proliferating normal and cancer cells
    L Chaudhuri
    Division of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ, USA
    Oncogene 31:1207-16. 2012
    ..We conclude that the 3'-UTR of MnSOD regulates MnSOD expression in response to different growth states and radiation...
  40. pmc Time course of congener uptake and elimination in rats after short-term inhalation exposure to an airborne polychlorinated biphenyl (PCB) mixture
    Xin Hu
    Interdisciplinary Graduate Program in Human Toxicology, Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa 52242, USA
    Environ Sci Technol 44:6893-900. 2010
    ..Selective uptake and elimination led to accumulation of a distinct congener spectrum in tissue. Minimal evidence of toxicity was observed...
  41. pmc Regulatory crosstalk and interference between the xenobiotic and hypoxia sensing pathways at the AhR-ARNT-HIF1α signaling node
    Sabine U Vorrink
    Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, USA Department of Radiation Oncology, The University of Iowa, Iowa City, IA, USA
    Chem Biol Interact 218:82-8. 2014
    ..We highlight studies that assess the role of ARNT, elucidate the mechanism of the crosstalk, and discuss the physiological implications for exposure to AhR-inducing compounds in the context of hypoxia. ..
  42. pmc Oxidation of polychlorinated biphenyls by liver tissue slices from phenobarbital-pretreated mice is congener-specific and atropselective
    Xianai Wu
    Department of Occupational and Environmental Health, College of Public Health and Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, Iowa 52242, United States
    Chem Res Toxicol 26:1642-51. 2013
    ..These species differences in the metabolism of chiral PCBs should be considered in developmental neurotoxicity studies of PCBs. ..
  43. pmc Selenoprotein P inhibits radiation-induced late reactive oxygen species accumulation and normal cell injury
    Jaimee C Eckers
    Free Radical and Radiation Biology Division, Department of Radiation Oncology, University of Iowa, Iowa City, Iowa
    Int J Radiat Oncol Biol Phys 87:619-25. 2013
    ..The purpose of this study was to investigate whether selenoprotein P (SEPP1), a major supplier of selenium to tissues and an antioxidant, regulates late ROS accumulation and toxicity in irradiated normal human fibroblasts (NHFs)...
  44. pmc Stereoselective formation of mono- and dihydroxylated polychlorinated biphenyls by rat cytochrome P450 2B1
    Zhe Lu
    Department of Chemistry, University of Manitoba, Winnipeg, MB, R3T 2N2, Canada
    Environ Sci Technol 47:12184-92. 2013
    ....
  45. pmc Chlorinated biphenyl quinones and phenyl-2,5-benzoquinone differentially modify the catalytic activity of human hydroxysteroid sulfotransferase hSULT2A1
    Xiaoyan Qin
    Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, Iowa 52242, United States
    Chem Res Toxicol 26:1474-85. 2013
    ..Equilibrium binding experiments and molecular modeling suggested that changes due to these modifications may affect the nucleotide binding site and the entrance to the sulfuryl acceptor binding site of hSULT2A1. ..
  46. pmc Structure-activity relationship of selected meta- and para-hydroxylated non-dioxin like polychlorinated biphenyls: from single RyR1 channels to muscle dysfunction
    Yassaman Niknam
    Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California 95616
    Toxicol Sci 136:500-13. 2013
    ..NDL-PCBs and their 5-OH and 4-OH metabolites differentially influence RyR1 channel activity and ECC in embryonic skeletal muscle...
  47. pmc A new player in environmentally induced oxidative stress: polychlorinated biphenyl congener, 3,3'-dichlorobiphenyl (PCB11)
    Yueming Zhu
    Free Radical and Radiation Biology Program, B180 Medical Laboratories, Department of Radiation Oncology, Holden Comprehensive Cancer Center
    Toxicol Sci 136:39-50. 2013
    ..Furthermore, antioxidant treatments following PCBs exposure could significantly mitigate the PCB-induced cytotoxicity in exponentially growing human prostate epithelial cells...
  48. pmc Sediment pore water distribution coefficients of PCB congeners in enriched black carbon sediment
    Andres Martinez
    Department of Civil and Environmental Engineering, IIHR Hydroscience and Engineering, The University of Iowa, 4105 Seamans Center, Iowa City, IA 52242, USA Electronic address
    Environ Pollut 182:357-63. 2013
    ..09 ± 0.06. Although black carbon content is very high in these sediments and was expected to play an important role in the distribution of PCBs, no improvement was obtained when a two-carbon model was used...
  49. pmc The concentration of glutathione in human erythrocytes is a heritable trait
    Thomas J van 't Erve
    Interdisciplinary Program in Human Toxicology, The University of Iowa, Iowa City, IA 52242, USA
    Free Radic Biol Med 65:742-9. 2013
    ..Understanding the genetic determinants of these inherited traits may allow personalized approaches to relevant therapies. ..
  50. pmc Flame retardant BDE-47 effectively activates nuclear receptor CAR in human primary hepatocytes
    Tatsuya Sueyoshi
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology and
    Toxicol Sci 137:292-302. 2014
    ..Our results indicate that BDE-47 induces CYP genes through activation of human CAR in addition to the previously identified pathway through human PXR. ..
  51. pmc The fate of inhaled (14)C-labeled PCB11 and its metabolites in vivo
    Xin Hu
    Department of Occupational and Environmental Health, University of Iowa, Iowa City, IA 52242, USA Electronic address
    Environ Int 63:92-100. 2014
    ..Some lower-chlorinated PCBs are still being produced and contaminate both indoor and ambient air...
  52. pmc The heritability of metabolite concentrations in stored human red blood cells
    Thomas J van 't Erve
    Interdisciplinary Program in Human Toxicology, The University of Iowa, Iowa City, Iowa
    Transfusion 54:2055-63. 2014
    ..However, this critical discovery has not been further explored. In a classic twin study we confirmed the heritability of poststorage ATP concentrations and established the heritability of many other RBC metabolites...
  53. pmc Binding interactions of hydroxylated polychlorinated biphenyls (OHPCBs) with human hydroxysteroid sulfotransferase hSULT2A1
    Edugie J Ekuase
    Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, United States
    Chem Biol Interact 212:56-64. 2014
    ..These results have implications for the roles of SULTs in the toxicology of OHPCBs, while also providing molecular probes of the complexity of substrate/inhibitor interactions with hSULT2A1. ..
  54. pmc Microsomal oxidation of 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) results in species-dependent chiral signatures of the hydroxylated metabolites
    Xianai Wu
    Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, Iowa, United States
    Environ Sci Technol 48:2436-44. 2014
    ..These differences in OH-PCBs' atropisomeric enrichment may not only be toxicologically relevant but may also be useful to study sources and transport of OH-PCBs in the environment. ..
  55. pmc Toxicity assessment of air-delivered particle-bound polybrominated diphenyl ethers
    Jong Sung Kim
    Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, UI Research Park, Iowa City, IA 52242 5000, USA Electronic address
    Toxicology 317:31-9. 2014
    ..The present study clearly indicates the potential of our exposure system for studying the toxicity of particle-bound compounds...
  56. pmc PCB 136 atropselectively alters morphometric and functional parameters of neuronal connectivity in cultured rat hippocampal neurons via ryanodine receptor-dependent mechanisms
    Dongren Yang
    Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California 95616
    Toxicol Sci 138:379-92. 2014
    ....
  57. pmc Hypoxia perturbs aryl hydrocarbon receptor signaling and CYP1A1 expression induced by PCB 126 in human skin and liver-derived cell lines
    Sabine U Vorrink
    Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, USA Department of Radiation Oncology, The University of Iowa, Iowa City, IA, USA
    Toxicol Appl Pharmacol 274:408-16. 2014
    ..Our results show that AhR activation and CYP1A1 expression induced by PCB 126 were significantly inhibited by hypoxia and hypoxia might therefore play an important role in PCB metabolism and toxicity. ..
  58. pmc Effective synthesis of sulfate metabolites of chlorinated phenols
    Hans Joachim Lehmler
    Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, IA 52242, USA Electronic address
    Chemosphere 93:1965-71. 2013
    ..The chlorophenol sulfates were stable for several months if stored at -20 °C and, thus, are useful for future toxicological, environmental and human biomonitoring studies...
  59. pmc 3,4',5-Trichloro-biphenyl-4-yl 2,2,2-trichloro-ethyl sulfate
    Hans Joachim Lehmler
    The University of Iowa, Department of Occupational and Environmental Health, Iowa City, IA 52242, USA
    Acta Crystallogr Sect E Struct Rep Online 69:o620. 2013
    ..The dihedral angles between the benzene rings in the two mol-ecules are 37.8 (2) and 35.0 (2)°...
  60. ncbi Dechlorination of PCBs in the rhizosphere of switchgrass and poplar
    Richard E Meggo
    Department of Civil and Environmental Engineering, 4105 Seamans Center, University of Iowa, IA 52242, USA
    Environ Pollut 178:312-21. 2013
    ..This is the first report of rhizosphere biotransformation pathways for reductive dechlorination in marginally aerobic, intermittently flooded soil as evidenced by a mass balance on transformation products...
  61. pmc Transformation of hydroxylated derivatives of 2,5-dichlorobiphenyl and 2,4,6-trichlorobiphenyl by Burkholderia xenovorans LB400
    Rouzbeh Tehrani
    Department of Civil and Environmental Engineering, Temple University, Philadelphia, PA, 19122, USA
    Environ Sci Pollut Res Int 21:6346-53. 2014
    ..The present study is significant because it provides evidence that PCB-degrading bacteria are capable of transforming hydroxylated derivatives of PCBs, which are increasingly considered as a new class of environmental contaminants. ..
  62. pmc Sulfated metabolites of polychlorinated biphenyls are high-affinity ligands for the thyroid hormone transport protein transthyretin
    Fabian A Grimm
    Interdisciplinary Graduate Program in Human Toxicology, Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, College of Public Health, The University of Iowa, Iowa City, Iowa 52246, USA
    Environ Health Perspect 121:657-62. 2013
    ..Previous research has discovered hydroxylated PCB metabolites (OH-PCBs) as high-affinity ligands for TTR, but the binding potential of conjugated PCB metabolites such as PCB sulfates has not been explored...
  63. pmc Elimination of inhaled 3,3'-dichlorobiphenyl and the formation of the 4-hydroxylated metabolite
    Xin Hu
    Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, Iowa 52242, USA
    Environ Sci Technol 47:4743-51. 2013
    ..4 h half-life. This study demonstrates rapid metabolism of CB11 and elimination of 4-OH-CB11 and suggests that the metabolite is not retained in the body but is susceptible to further biotransformation...
  64. pmc Metabolism of 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) atropisomers in tissue slices from phenobarbital or dexamethasone-induced rats is sex-dependent
    Xianai Wu
    Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, IA, USA
    Xenobiotica 43:933-47. 2013
    ..4. Our results suggest that enantioselective metabolism, sex and induction status of P450 enzymes in the liver may modulate the neurotoxic outcomes of developmental exposure to chiral PCBs...
  65. pmc Cyclic siloxanes in air, including identification of high levels in Chicago and distinct diurnal variation
    Rachel A Yucuis
    Department of Civil and Environmental Engineering, IIHR Hydroscience and Engineering, University of Iowa, Iowa City, IA 52242, USA
    Chemosphere 92:905-10. 2013
    ..D5 was the dominant siloxane in both indoor and outdoor air. Ratios of D5 to D4 averaged 91 and 3.2 for indoor and outdoor air respectively...
  66. pmc The effects of 3,3',4,4'-tetrabromobiphenyl on rats fed diets containing a constant level of copper and varying levels of molybdenum
    Kadhim N Salman
    Graduate Center for Toxicology, University of Kentucky, Lexington, KY, 40536, USA
    Environ Sci Pollut Res Int 21:6400-9. 2014
    ....
  67. pmc Hydroxylated polychlorinated biphenyls in the environment: sources, fate, and toxicities
    Rouzbeh Tehrani
    Department of Civil and Environmental Engineering, Temple University, Philadelphia, PA, 19122, USA
    Environ Sci Pollut Res Int 21:6334-45. 2014
    ..This article reviews recent findings regarding the sources, fate, and toxicities of OH-PCBs in the environment. ..
  68. pmc Dietary antioxidants (selenium and N-acetylcysteine) modulate paraoxonase 1 (PON1) in PCB 126-exposed rats
    Hua Shen
    Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, USA
    Environ Sci Pollut Res Int 21:6384-99. 2014
    ..These interactions should be further explored in the development of dietary protection regimens...
  69. pmc Discovery of hydroxylated polychlorinated biphenyls (OH-PCBs) in sediment from a lake Michigan waterway and original commercial aroclors
    Rachel F Marek
    Department of Civil and Environmental Engineering and IIHR Hydroscience and Engineering, The University of Iowa, Iowa City, Iowa, 52242, United States
    Environ Sci Technol 47:8204-10. 2013
    ..We are the first to report levels of OH-PCBs in sediment and Aroclors, and our discovery is significant because it is likely that OH-PCB contamination exists in sediment anywhere that PCB contamination from Aroclors is present. ..
  70. pmc Simulating and explaining passive air sampling rates for semivolatile compounds on polyurethane foam passive samplers
    Nicholas T Petrich
    Department of Civil and Environmental Engineering, The University of Iowa, Iowa City, Iowa 52242, United States
    Environ Sci Technol 47:8591-8. 2013
    ..3%). ..
  71. pmc Phytotechnologies--preventing exposures, improving public health
    Heather F Henry
    Superfund Research Program, National Institute of Environmental Health Sciences, PO Box 12233 K 304, Research Triangle Park, NC 27709, USA
    Int J Phytoremediation 15:889-99. 2013
    ..Hence, phytotechnologies may provide sustainable solutions to environmental exposure challenges, improving public health and potentially reducing the burden of disease...
  72. pmc Chlordane and heptachlor are metabolized enantioselectively by rat liver microsomes
    Izabela Kania-Korwel
    Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, Iowa, USA
    Environ Sci Technol 47:8913-22. 2013
    ..These findings demonstrate that the direction and extent of the enantioselective metabolism of both chlordane isomers and heptachlor is P450 isoform-dependent and can be modulated by the induction of P450 enzymes. ..
  73. pmc 2,2',5',6-Tetra-chloro-4-[(1S)-1-methyl-prop-oxy]biphen-yl
    Hans Joachim Lehmler
    The University of Iowa, Department of Occupational and Environmental Health, Iowa City, IA 52242 5000, USA
    Acta Crystallogr Sect E Struct Rep Online 69:o983. 2013
    ..In the title mol-ecule, C16H14Cl4O, the dihedral angle between the least-square planes of the benzene rings is 84.40 (7)°. No unusual intermolecular interactions are present. ..
  74. pmc Manganoporphyrins increase ascorbate-induced cytotoxicity by enhancing H2O2 generation
    Malvika Rawal
    Department of Radiation Oncology, The University of Iowa Carver College of Medicine, Iowa City, IA, USA
    Cancer Res 73:5232-41. 2013
    ..Finally, tumor growth in vivo was inhibited more effectively by combining MnT4MPyP with AscH-. We concluded that MnPs increase the rate of oxidation of AscH- to leverage H2O2 flux and ascorbate-induced cytotoxicity...
  75. pmc Chronic chlorpyrifos exposure does not promote prostate cancer in prostate specific PTEN mutant mice
    Robert U Svensson
    Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA
    J Environ Pathol Toxicol Oncol 32:29-39. 2013
    ....
  76. pmc 5,5'-Dichloro-2,2'-dimeth-oxy-biphen-yl
    Hans Joachim Lehmler
    The University of Iowa, Department of Occupational and Environmental Health, Iowa City, IA 52242 5000, USA
    Acta Crystallogr Sect E Struct Rep Online 69:o650. 2013
    ..17 (6)°. Both meth-oxy groups are slightly out of the plane of the benzene rings to which they are attached, making dihedral angles of 4.22 (18) and 18.82 (16)°...
  77. pmc Sulfate conjugates are urinary markers of inhalation exposure to 4-chlorobiphenyl (PCB3)
    Kiran Dhakal
    Interdisciplinary Graduate Program in Human Toxicology and Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa 52242, USA
    Chem Res Toxicol 26:853-5. 2013
    ..PCB sulfates were stable in urine for at least three days at room temperature without chemical preservatives. These data support the use of PCB sulfate conjugates as suitable urinary biomarkers of PCB3 and other airborne PCBs...
  78. pmc Does dietary copper supplementation enhance or diminish PCB126 toxicity in the rodent liver?
    Ian K Lai
    Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, UI Research Park, 219 IREH, Iowa City, Iowa 52242 5000, USA
    Chem Res Toxicol 26:634-44. 2013
    ..PCB126 toxicity, i.e., oxidative stress and steatosis, is clearly associated with disturbed metal homeostasis. Understanding the mechanisms of this disturbance may provide tools to prevent liver toxicity by other AhR agonists...
  79. pmc Thermodynamic and kinetic considerations for the reaction of semiquinone radicals to form superoxide and hydrogen peroxide
    Yang Song
    College of Pharmaceutical Sciences, Key Laboratory of Eco environments in Three Gorges Reservoir Region, Ministry of Education, Southwest University, Chongqing, 400715, People s Republic of China
    Free Radic Biol Med 49:919-62. 2010
    ..The rate constants for these addition reactions are also related to E degrees'. Thus, pK(a)'s of a hydroquinone and E degrees ' are central to the chemistry of these triads...
  80. pmc Oxidation of 4-chlorobiphenyl metabolites to electrophilic species by prostaglandin H synthase
    Orarat Wangpradit
    Department of Occupational and Environmental Health, Interdisciplinary Graduate Program in Human Toxicology, College of Pharmacy, and Seamans Center for the Engineering Art and Sciences, University of Iowa, Iowa City, Iowa 52242, USA
    Chem Res Toxicol 22:64-71. 2009
    ....
  81. pmc Pentachlorophenol and other chlorinated phenols are substrates for human hydroxysteroid sulfotransferase hSULT2A1
    Hayrettin Ozan Gulcan
    Division of Medicinal and Natural Products Chemistry, College of Pharmacy, The University of Iowa, Iowa City, Iowa 52242, USA
    Chem Res Toxicol 21:1503-8. 2008
    ..Thus, the sulfation of polychlorinated phenols catalyzed by hSULT2A1 may be a significant component of their metabolism in humans...
  82. pmc Inhibition of the promotion of hepatocarcinogenesis by 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) by the deletion of the p50 subunit of NF-kappa B in mice
    Howard P Glauert
    Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY 40506, USA
    Toxicol Appl Pharmacol 232:302-8. 2008
    ..Taken together, these data indicate that the absence of the NF-kappaB p50 subunit inhibits the promoting activity of PCB-153 and alters the proliferative and apoptotic changes in mouse liver in the response to PCBs...
  83. pmc Semiquinone radicals from oxygenated polychlorinated biphenyls: electron paramagnetic resonance studies
    Yang Song
    Department of Occupational and Environmental Health, The University of Iowa, Iowa City, Iowa 52242 1101, USA
    Chem Res Toxicol 21:1359-67. 2008
    ..Our data also point to futile redox cycling as being one mechanism by which oxygenated PCBs can lead to the formation of reactive oxygen species, but this is most efficient in the presence of SOD...
  84. pmc 2,2',3,3',6,6'-Hexachlorobiphenyl (PCB 136) atropisomers interact enantioselectively with hepatic microsomal cytochrome P450 enzymes
    Izabela Kania-Korwel
    Department of Occupational and Environmental Health, University of Iowa, 100 Oakdale Campus 124 IREH, Iowa City, Iowa 52242, USA
    Chem Res Toxicol 21:1295-303. 2008
    ....
  85. pmc Metabolic Activation of PCBs to Carcinogens in Vivo - A Review
    Gabriele Ludewig
    Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, IA 52242, USA
    Environ Toxicol Pharmacol 25:241-6. 2008
    ..4-HO-PCB3 caused a non-significant (p = 0.115) doubling of the MF compared to the control. These studies prove that lower halogenated biphenyls may be metabolically activated in vivo to genotoxic and initiating intermediates...
  86. pmc Mutagenicity of 3-methylcholanthrene, pcb3, and 4-oh-pcb3 in the lung of transgenic bigblue rats
    Catherine Maddox
    Dept Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, IA, USA
    Environ Toxicol Pharmacol 25:260-6. 2008
    ....
  87. ncbi Enantiomeric enrichment of 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) in mice after induction of CYP enzymes
    Izabela Kania-Korwel
    Department of Occupational and Environmental Health, University of Iowa, College of Public Health, 100 Oakdale Campus, 114 IREH, Iowa City, IA 52242, USA
    Arch Environ Contam Toxicol 55:510-7. 2008
    ..Overall, this study does not support the hypothesis that metabolism by CYP2B enzymes is responsible for the enrichment of (+)-PCB 136 in mice...
  88. ncbi Xenobiotic geometry and media pH determine cytotoxicity through solubility
    Gregor Luthe
    Department of Occupational and Environmental Health, University of Iowa, 100 Oakdale Campus, Iowa City, Iowa 52242 5000, USA
    Chem Res Toxicol 21:1017-27. 2008
    ..We suggest that pH-driven changes in the tertiary and quaternary structure of albumin are responsible. These observations have implications for studies of the biological activity of semisoluble compounds, like PCBs and related compounds...
  89. pmc Catalase ameliorates polychlorinated biphenyl-induced cytotoxicity in nonmalignant human breast epithelial cells
    Venkatasubbaiah A Venkatesha
    Free Radical and Radiation Biology Program, B180 Medical Laboratories, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242 1181, USA
    Free Radic Biol Med 45:1094-102. 2008
    ..Our results demonstrate a PCB-induced increase in cellular levels of ROS causing DNA damage, resulting in cell killing...
  90. pmc Gas chromatographic separation of methoxylated polychlorinated biphenyl atropisomers
    Izabela Kania-Korwel
    Department of Occupational and Environmental Health, University of Iowa, 124 IREH, Iowa City, IA 52242, USA
    J Chromatogr A 1207:146-54. 2008
    ..The methylated derivatives of two OH-PCB 136 metabolites showed an enantiomeric enrichment in liver tissue, whereas PCB 136 itself was near racemic...

Research Grants30

  1. EPIDEMIOLOGY OF ALCOHOL PROBLEMS
    Thomas K Greenfield; Fiscal Year: 2013
    ..We plan to build research capacity in the Center and other organizations, enhance careers of new investigators, and make key findings accessible to researchers, policy makers, practitioners, and the public. ..
  2. Elucidating Risks: From Exposure and Mechanism to Outcome
    James A Swenberg; Fiscal Year: 2013
    ..This Program is highly relevant to Superfund by addressing high-priority chemicals and by focusing on mechanisms underlying health effects, exposure assessment, and remediation to mitigate exposure and toxicity. ..