ToxSci Advance Access published online on September 26, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfg233
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
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1 University at Albany, School of Public Health, Department of Environmental Health and Toxicology, Rensselaer NY 12144
* To whom correspondence should be addressed. E-mail: Carpent{at}uamail.albany.edu.
The effects of exposure of acutely dissociated rat thymocytes to various polychlorinated biphenyl (PCB) congeners were examined using flow cytometry. Non-planar, ortho-substituted congeners caused a rapid cell death at low micromolar concentrations, while coplanar, dioxin-like congeners at the same concentration were without significant effect. The most potent of the congeners studied was PCB 52 (2,2',5,5'-tetrachlorobiphenyl), which had an IC50 of 3.96 µM at 20 minutes. Prior to loss of viability there was a decrease in mitochondrial membrane potential (
© 2003 Society of Toxicology
Neurotoxicology
Ortho-Substituted PCBs Kill Thymocytes
2 University at Albany, School of Public Health, Dept. of Environmental Health and Toxicology, Rensselaer NY 12144
3 New York State Department of Health, Wadsworth Center, Albany NY 12203
4 New York State Department of Health, Wadsworth Center, Albany NY 12203; University at Albany, School of Public Health, Department of Environmental Health and Toxicology, Rensselaer NY 12144
5 University at Albany, Institute for Health and the Environment and School of Public Health, Department of Environmental Health and Toxicology, Rensselaer NY 12144
Abstract 
m), an accumulation of intracellular calcium, and a progressive leakiness of the plasma membrane. Application of PCB 52 in calcium-free medium reduced the calcium accumulation, but did not reduce cell death. Agents which depolarized mitochondria also did not induce the same degree of cell death caused by PCB 52. Cyclosporin A, which prevents opening of the mitochondria permeability transition channel, protected against cell death but did not protect against mitochondrial depolarization or calcium accumulation. Rapamycin and FK 506 at high concentration provided partial protection against cell death. These observations indicate that the ortho-substituted PCB 52 disrupts plasma, mitochondrial and endoplasmic reticulum membranes. We hypothesize that PCB 52 incorporates into lipid bilayers and with its bulky, three dimensional ortho-substituted congener structure disrupts membrane function to a greater degree than coplanar congeners.
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