| Polychlorinated Biphenyls and Methylmercury Act Synergistically to Reduce Rat Brain Dopamine Content in Vitro Jeffrey C. Bemis1 and Richard F. Seegal1,2 1School of Public Health, University at Albany, Albany, New York, USA; 2New York State Department of Health, Wadsworth Center, Albany, New York, USA Abstract
Consumption of contaminated Great Lakes fish by pregnant women is associated with decreased birth weight and deficits in cognitive function in their infants and children. These fish contain many known and suspected anthropogenic neurotoxicants, making it difficult to determine which contaminant(s) are responsible for the observed deficits. We have undertaken a series of experiments to determine the relevant toxicants by comparing the neurotoxic effects of two of these contaminants--polychlorinated biphenyls (PCBs) and methylmercury (MeHg) --both of which are recognized neurotoxicants. Striatal punches obtained from adult rat brain were exposed to PCBs only, MeHg only, or the two in combination, and tissue and media concentrations of dopamine (DA) and its metabolites were determined by high performance liquid chromatography. Exposure to PCBs only reduced tissue DA and elevated media DA in a dose-dependent fashion. Exposure to MeHg only did not significantly affect either measure. However, when striatal punches were simultaneously exposed to PCBs and MeHg, there were significantly greater decreases in tissue DA concentrations and elevations in media DA than those caused by PCBs only, in the absence of changes in media lactate dehydrogenase concentrations. Elevations in both tissue and media 3,4-dihydroxyphenylacetic acid concentrations were also observed. We suggest that the significant interactions between these two toxicants may be due to a common site of action (i.e., toxicant-induced increases in intracellular calcium and changes in second messenger systems) that influences DA function. The synergism between these contaminants suggests that future revisions of fish-consumption guidelines should consider contaminant interactions. Key words: dopamine, methylmercury, polychlorinated biphenyls, rat brain, striatal slice, synergism. Environ Health Perspect 107:879-885 (1999) . [Online 7 October 1999] http://ehpnet1.niehs.nih.gov/docs/1999/107p879-885bemis/ abstract.html Address correspondence to R.F. Seegal, New York State Department of Health, Wadsworth Center, Box 509, Albany NY 12201-0509. Telephone: (518) 473-4378. Fax: (518) 486-1505. E-mail: seegal@wadsworth.org Research support for this work was provided in part by NIEHS Superfund Basic Research Program grant P42 ES04913 and NIEHS grant R01 ES07921 to R.F. Seegal. Received 2 March 1999 ; accepted 24 June 1999.
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