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Journal Article 
A non-coplanar polychlorinated biphenyl induces oxidative stress and cell death in a mid-brain dopaminergic cell line 
Seegal, RF; Kanthasamy, AG; Kaul, S 
ISSN: 0731-9193 
Polychlorinated biphenyls (PCBs) are associated with developmental deficits in children and behavioral and neurochemical changes in laboratory animals. Following in vivo and in vitro exposure PCBs reduce dopamine (DA) concentrations and elevate intra-neuronal or media concentrations of DA. These changes may be mediated by inhibition of monoamine transporters, including the DA transporter and the vesicular monoamine transporter. To better understand the consequences of PCB exposure on neuronal function, we exposed the rat mesencephalic dopaminergic neuronal cell line (N27) to a non-coplanar PCB congener (2, 3, 6, 2?, 5?-PtCB, 10, 30 and 100 ?M) and measured changes in oxidative stress (using dihydroethidine and flow cytometry) and cell death (using the Sytox Green Cytotoxicity assay). PtCB resulted in significant time and dose dependent increases in ROS formation with elevations seen at 30 and 100 ?M and as early as five min after exposure. Pretreatment with a cell permeable superoxide dismutase mimetic MnTBAP (5 ?M for 15 min) significantly attenuated PtCB-induced ROS production, indicating that PtCB predominantly generates superoxide species. Cell death was measured in serum free media following 1, 2 or 4 hr exposure to PtCB with significant elevations seen at 30 and 100 ? M after 2 and 4 hr. These results demonstrate that ROS formation occurs prior to cell death and may thus contribute to loss of cell viability. Most importantly, PtCB induced ROS formation in N27 cells was greater than that reported following exposure to the same concentrations of MPP+, the active metabolite of MPTP. Taken together, these results provide continuing support for the hypothesis that PCBs may contribute to mid-brain DA neuronal cell loss and thus ultimately play a role in the etiology of parkinsonism. 
43rd Annual Society of Toxicology ToxExpo 
Baltimore, MD 
March 21-25, 2004 
• PCBs
          LitSearch August 2015