Polychlorinated biphenyls (PCBs) are metabolized in humans and other mammals to hydroxylated derivatives (OHPCBs) that are increasingly recognized as having significant roles in the retention of, and toxic responses to, these environmental contaminants. OHPCBs interact with cytosolic sulfotransferases (SULTs) as substrates and inhibitors, and the effects of these interactions on the toxicities of these molecules depend upon the structure of the OHPCB and the isoform(s) of SULT involved. The long term goal of Project 3 is to better understand relationships between the regulation of catalytic function of SULTs and the biological activities of OHPCBs derived from semi-volatile PCBs. The primary objectives of the work proposed for the next project period are to address gaps in our knowledge related to structure-activity relationships of OHPCBs with the family 2 (also known as hydroxysteroid or alcohol) SULTs, to elucidate how the oxidative environments of both family 1 and family 2 SULTs regulate their interactions with OHPCBs, and to understand the properties of the sulfuric acid esters of OHPCBs formed in SULT-catalyzed reactions. The central hypothesis for Project 3 is that OHPCBs serve as substrates and inhibitors of both family 1 and family 2 SULTs, and that the interactions of individual OHPCBs with these enzymes are significantly altered in a predictable manner by oxidation of thiols in these enzymes. Moreover, a corollary hypothesis is that the sulfated OHPCB-metabolites have toxicologically important chemical and biochemical properties.
The specific aims to be investigated during the next five-year period are: 1) to study the structure-activity relationships for OHPCBs as inhibitors and substrates of human hydroxysteroid sulfotransferase hSULT2A1;2) to explore the roles that the oxidation of thiols in SULTs play in regulation of their specificity for OHPCBs as inhibitors and substrates;and 3) to understand the properties of the sulfuric acid esters derived from sulfation of OHPCBs. This research will yield significant new fundamental insight into the interactions of OHPCBs with SULTs, and the potential consequences of these interactions for sulfation of endogenous molecules as well as xenobiotics.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
Application #
Study Section
Special Emphasis Panel (ZES1-LWJ-M)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Iowa
Iowa City
United States
Zip Code
Wu, Xianai; Yang, Jun; Morisseau, Christophe et al. (2016) 3,3',4,4',5-Pentachlorobiphenyl (PCB 126) Decreases Hepatic and Systemic Ratios of Epoxide to Diol Metabolites of Unsaturated Fatty Acids in Male Rats. Toxicol Sci 152:309-22
Martinez, Andres; Schnoebelen, Douglas J; Hornbuckle, Keri C (2016) Polychlorinated biphenyl congeners in sediment cores from the Upper Mississippi River. Chemosphere 144:1943-9
Xin, Xing; Senthilkumar, P K; Schnoor, Jerald L et al. (2016) Effects of PCB126 and PCB153 on telomerase activity and telomere length in undifferentiated and differentiated HL-60 cells. Environ Sci Pollut Res Int 23:2173-85
Wangpradit, Orarat; Adamcakova-Dodd, Andrea; Heitz, Katharina et al. (2016) PAMAM dendrimers as nano carriers to investigate inflammatory responses induced by pulmonary exposure of PCB metabolites in Sprague-Dawley rats. Environ Sci Pollut Res Int 23:2128-37
Koh, Wen Xin; Hornbuckle, Keri C; Wang, Kai et al. (2016) Serum polychlorinated biphenyls and their hydroxylated metabolites are associated with demographic and behavioral factors in children and mothers. Environ Int 94:538-45
Osterberg, David; Scammell, Madeleine Kangsen (2016) PCBs in schools--where communities and science come together. Environ Sci Pollut Res Int 23:1998-2002
Herkert, Nicholas J; Martinez, Andres; Hornbuckle, Keri C (2016) A Model Using Local Weather Data to Determine the Effective Sampling Volume for PCB Congeners Collected on Passive Air Samplers. Environ Sci Technol 50:6690-7
Li, Miao; Teesch, Lynn M; Murry, Daryl J et al. (2016) Cytochrome c adducts with PCB quinoid metabolites. Environ Sci Pollut Res Int 23:2148-59
Wangpradit, Orarat; Rahaman, Asif; Mariappan, S V Santhana et al. (2016) Breaking the dogma: PCB-derived semiquinone free radicals do not form covalent adducts with DNA, GSH, and amino acids. Environ Sci Pollut Res Int 23:2138-47
Flor, Susanne; He, Xianran; Lehmler, Hans-Joachim et al. (2016) Estrogenicity and androgenicity screening of PCB sulfate monoesters in human breast cancer MCF-7 cells. Environ Sci Pollut Res Int 23:2186-200

Showing the most recent 10 out of 248 publications