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Ellen Fritsche,¹ Jason E. Cline,¹ Ngoc-Ha Nguyen,² Thomas S. Scanlan,² and Josef Abel¹

¹Group of Toxicology, Institut für umweltmedizinische Forschung gGmbH an der Heinrich-Heine Universität, Düsseldorf, Germany; ²Departments of Pharmaceutical Chemistry and Cellular and Molecular Pharmacology, University of California-San Francisco, San Francisco, California, USA

Abstract
Polychlorinated biphenyls (PCBs) are ubiquitous environmental chemicals that accumulate in adipose tissues over the food chain. Epidemiologic studies have indicated that PCBs influence brain development. Children who are exposed to PCBs during development suffer from neuropsychologic deficits such as a lower full-scale IQ (intelligence quotient) , reduced visual recognition memory, and attention and motor deficits. The mechanisms leading to these effects are not fully understood. It has been speculated that PCBs may affect brain development by interfering with thyroid hormone (TH) signaling. Because most of the data are from animal studies, we established a model using primary normal human neural progenitor (NHNP) cells to determine if PCBs interfere with TH-dependent neural differentiation. NHNP cells differentiate into neurons, astrocytes, and oligodendrocytes in culture, and they express a variety of drug metabolism enzymes and nuclear receptors. Like triiodothyronine (T₃) , treatment with the mono-ortho-substituted PCB-118 (2,3“,4,4“,5-pentachlorobiphenyl ; 0.01-1 µM) leads to a dose-dependent increase of oligodendrocyte formation. This effect was congener specific, because the coplanar PCB-126 (3,3“,4,4“,5-pentachlorobiphenyl) had no effect. Similar to the T₃ response, the PCB-mediated effect on oligodendrocyte formation was blocked by retinoic acid and the thyroid hormone receptor antagonist NH-3. These results suggest that PCB-118 mimics T₃ action via the TH pathway. Key words: NH-3, NHNP cells, oligodendrocyte, PCB, retinoic acid, thyroid hormone receptors. Environ Health Perspect 113:871-876 (2005) . doi:10.1289/ehp.7793 available via http://dx.doi.org/ [Online 18 April 2005]

Address correspondence to E. Fritsche, Institut für umweltmedizinische Forschung, Auf'm Hennekamp 50, 40225 Düsseldorf, Germany. Telephone 49-211-3389203. Fax: 49-211-3190910. E-mail: ellen.fritsche@uni-duesseldorf.de

We thank U. Krämer for her help with the statistics.

This work was supported by the Bundesministerium für Umwelt (BMU B1) , and by a grant from the U.S. National Institutes of Health (DK52798) .

The authors declare they have no competing financial interests.

Received 25 November 2004 ; accepted 18 April 2005.