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.

National Institute of Health (NIH)
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
Application #
Study Section
Special Emphasis Panel (ZES1)
Program Officer
Henry, Heather F
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Iowa
Public Health & Prev Medicine
Schools of Public Health
Iowa City
United States
Zip Code
Liang, Yi; Meggo, Richard; Hu, Dingfei et al. (2014) Enhanced Polychlorinated Biphenyl Removal in a Switchgrass Rhizosphere by Bioaugmentation with Burkholderia xenovorans LB400. Ecol Eng 71:215-222
Yang, Shupeng; Shi, Weimin; Hu, Dingfei et al. (2014) In vitro and in vivo metabolite profiling of valnemulin using ultraperformance liquid chromatography-quadrupole/time-of-flight hybrid mass spectrometry. J Agric Food Chem 62:9201-10
Salman, Kadhim N; Stuart, Mary A; Schmidt, Jack et al. (2014) The effects of 3,3',4,4'-tetrabromobiphenyl on rats fed diets containing a constant level of copper and varying levels of molybdenum. Environ Sci Pollut Res Int 21:6400-9
Tehrani, Rouzbeh; Lyv, Monica M; Van Aken, Benoit (2014) Transformation of hydroxylated derivatives of 2,5-dichlorobiphenyl and 2,4,6-trichlorobiphenyl by Burkholderia xenovorans LB400. Environ Sci Pollut Res Int 21:6346-53
Vorrink, Sabine U; Severson, Paul L; Kulak, Mikhail V et al. (2014) Hypoxia perturbs aryl hydrocarbon receptor signaling and CYP1A1 expression induced by PCB 126 in human skin and liver-derived cell lines. Toxicol Appl Pharmacol 274:408-16
Ekuase, Edugie J; Lehmler, Hans-Joachim; Robertson, Larry W et al. (2014) Binding interactions of hydroxylated polychlorinated biphenyls (OHPCBs) with human hydroxysteroid sulfotransferase hSULT2A1. Chem Biol Interact 212:56-64
Wu, Xianai; Kammerer, Austin; Lehmler, Hans-Joachim (2014) Microsomal oxidation of 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) results in species-dependent chiral signatures of the hydroxylated metabolites. Environ Sci Technol 48:2436-44
Shen, Hua; Li, Miao; Wang, Bingxuan et al. (2014) Dietary antioxidants (selenium and N-acetylcysteine) modulate paraoxonase 1 (PON1) in PCB 126-exposed rats. Environ Sci Pollut Res Int 21:6384-99
Hu, Xin; Adamcakova-Dodd, Andrea; Thorne, Peter S (2014) The fate of inhaled (14)C-labeled PCB11 and its metabolites in vivo. Environ Int 63:92-100
Sueyoshi, Tatsuya; Li, Linhao; Wang, Hongbing et al. (2014) Flame retardant BDE-47 effectively activates nuclear receptor CAR in human primary hepatocytes. Toxicol Sci 137:292-302

Showing the most recent 10 out of 171 publications