Polychlorinated Biphenyls and Methylmercury Act Synergistically to Reduce Rat Brain Dopamine Content in Vitro

Abstract

Consumption of contaminated Great 1Las 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, makdig 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 neurotouic efifect of two of these contaminants-polychorinated biphenyls (PCBs) and metylmercury (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 changs in media lacte 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 contamiants suggets that future revisions of fish-consumption guidelines should consider contaminat interactions. Key wordk. dopamine, methyimercury, polychlorinated biphenyls, rat brain, striatal slice, synergism.

Neonatal co-exposure to low doses of an ortho-PCB (PCB 153) and methyl mercury exacerbate defective developmental neurobehavior in mice

“…Although we did not use enough different concentrations for the doses to statistically distinguish between additive or synergistic effects, the present data plus our earlier data on PCB 153 and MeHg suggest that PCB 153 and MeHg can act synergistic in the low-dose range, but not in the high dose range. This is in agreement with the in vitro studies by Bemis and Seegal (1999) that have shown significantly altered dopamine concentrations from coexposure to PCB plus MeHg compared to PCB alone or MeHg alone.…”

“…Interactions between PCB and MeHg have been shown to act synergistically on the dopamine content in striatal brain punches in vitro studies (Bemis and Seegal, 1999). Recent in vivo studies indicate that developmental co-exposure of rats both to an ortho-substituted PCB (PCB 153) and MeHg can induce motor behavioral defects (Roegge et al, 2004).…”

An in vitro approach to assess the toxicity of certain food contaminants: Methylmercury and polychlorinated biphenyls

“…Both are fish contaminants, and the possibility of an interaction, leading to synergistic adverse effects, had been suggested by earlier experiments in vitro and in animals (Bemis and Seegal, 1999;Roegge et al, 2004), and by observations in humans (Grandjean et al, 2001;Stewart et al, 2003). By utilizing an effect additivity approach, as indicated by Lau et al (2006), we found no interactions among MeHg, PCB 126 and PCB 153 (Fig.…”

“…(2) To assess possible interactions between MeHg and PCBs. This was prompted by epidemiological, animal, and in vitro evidence which suggested a possible synergistic interaction between these compounds (Grandjean et al, 2001;Bemis and Seegal, 1999;Roegge et al, 2004). (3) To determine whether neurons with genetically modified glutathione (GSH) levels may be exploited as a screening tool for further mechanistic studies.…”

Mechanisms involved in the neurotoxic effects of environmental toxicants such as polychlorinated biphenyls and brominated flame retardants

“…Polychlorinated biphenyl and MeHg act synergistically on the DA content in striatal brain punches in vitro (Bemis and Seegal 1999). Exposure to the PCB mixtures A1254 and A1260 (10-200 ppm) only, reduced tissue DA and elevated media DA in a dose-dependent fashion.…”