Effect of In Utero Exposure to PCB 136 (2,2',3,3',6,6'- Hexachlorobiphenyl) Enantiomers on Neurodevelopmental Outcomes in Adult Offspring
Polychlorinated biphenyls (PCBs) are a group of industrial chemicals that persist in the environment and cause adverse neurodevelopmental effects (such as altered brain ryanodine binding) in laboratory animals and in humans. Several neurotoxic PCB congeners, such as PCB 136, are chiral and, as we have shown recently, sensitize ryanodine receptors in an enantiospecific manner in vitro. We hypothesize that exposure to PCB 136 during gestation and lactation causes long-term neurodevelopmental effects in an enantiomer specific manner, with (-)-PCB 136 being more potent and efficacious than (+)-PCB 136. This hypothesis will be tested by investigating enantiomer specific differences (1) in the profile of PCB 136 and its metabolites and (2) brain ryanodine binding in mice exposed during gestation and lactation to (+)- and (-)-PCB 136.
Kania-Korwel I, El-Komy MHME, Veng-Pedersen P, Lehmler HJ. Clearance of polychlorinated biphenyl atropisomers is enantioselective in female C57Bl/6 mice. Environ Sci Technol. 2010; 44:2828-2835.
Kania-Korwel I, Duffel MW, Lehmler HJ. Gas chromatographic analysis with chiral cyclodextrin phases reveals the enantioselective formation of hydroxylated polychlorinated biphenyls by rat liver microsomes. Environ Sci Technol. 2011 45:9590-9596.
Kania-Korwel I, Barnhart CD, Stamou M, Truong KM, El-Komy MHME, Lein PJ, Veng-Pedersen P, Lehmler HJ. 2,2',3,5',6-pentachlorobiphenyl (PCB95) and its hydroxylated metabolites are enantiomerically enriched in female mice. Environ Sci Technol. 2012; 46:11393-11401.
Kania-Korwel I, Lehmler HJ. Assigning atropisomer elution orders using atropisomerically enriched polychlorinated biphenyl fractions generated by microsomal metabolism. J Chromat A. 2012;1278:133-144.
Kania-Korwel I, Barnhart CD, Lein PJ, Lehmler HJ. Effect of pregnancy on the disposition of 2,2',3,5',6-pentachlorobiphenyl (PCB 95) atropisomers and their hydroxylated metabolites in female mice. Chem Res Toxicol. 2015; 28:1774-1783.