Grantee Research Project Results

2002 Progress Report: Developmental Effects of PCBs and Methylmercury

EPA Grant Number: R829390C004
Subproject: this is subproject number 004 , established and managed by the Center Director under grant R829390
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: CECEHDPR - University of Illinois FRIENDS Children’s Environmental Health Center
Center Director: Schantz, Susan L.
Title: Developmental Effects of PCBs and Methylmercury
Investigators: Seegal, Richard F. , Lawrence, David A. , Snyder-Keller, Abigail M.
Current Investigators: Seegal, Richard F.
Institution: New York State Department of Health
EPA Project Officer: Hahn, Intaek
Project Period: October 17, 2001 through October 16, 2002
Project Period Covered by this Report: October 17, 2001 through October 16, 2002
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2001) RFA Text |  Recipients Lists
Research Category: Children's Health , Human Health

Objective:

Determine the neurochemical and neuropathological consequences of developmental exposure of the laboratory rat to polychlorinated biphenyls (PCBs), methylmercury (MeHg) or the two neurotoxicants in combination. These data may aid in explaining the associations that have been observed between maternal consumption of fish contaminated with these and other toxicants and neurobehavioral deficits in their infants and children.

Progress Summary:

The experiments that provided the intellectual focus for the Children=s Health Center Grant demonstrated that polychlorinated biphenyls (PCBs) and methylmercury (MeHg) interact synergistically to alter dopamine (DA) function in striatal tissue derived from adult rats [1] and, in a time and dose dependent fashion, to either synergistically or antagonistically alter regulation of intra-cellular calcium concentrations in cerebellar granule cells obtained from early postnatal animals [2]. Although there are many differences between these two preparations that may explain the divergent results (e.g., the endpoint, the duration of exposure, the complexity of the neuronal preparation), one major difference is the age of the donor animal.

In order to determine whether the developmental status of the donor animal is a major factor in influencing the neurochemical responses to PCBs and MeHg we have exposed striatal tissue from early postnatal rats to PCBs and MeHg and measured changes in tissue DA concentrations. Striatal tissue, obtained from naive postnatal day (PND) 7, 14, 21 and 35 male rats, was exposed, ex vivo, to PCBs (5 to 100 ppm), MeHg (4 to 14 µM) or the two contaminants in combination for four hours.

The consequences of ex vivo exposure to PCBs was dependent on the age of the animal. As seen previously [1], tissue from adult rats exhibited a robust dose-dependent decrease in tissue DA concentrations. However, exposure of striatal tissue from PND 7, 14, and particularly PND 21 animals to PCBs, resulted in significantly less change in tissue DA concentrations than seen in tissue derived from adult rats.

Tissue DA concentrations, following exposure to MeHg, were again dependent on the age of the donor animal. However, unlike the greater decreases in tissue DA seen in PND 35 and adult tissue exposed to PCBs, the greatest MeHg-induced decreases in tissue DA concentrations occurred in tissue from younger animals.

Co-exposure of striatal tissue from PND 7-35 to PCBs and MeHg resulted in dose-dependent decreases in tissue DA concentrations that were greater than following exposure to either contaminant alone. However, unlike the synergistic decreases in tissue DA seen in tissue derived from adult rats, the PCB/MeHg induced reductions in tissue DA appear to be additive, rather than synergistic.

These results, obtained ex vivo, begin to provide information on the possible differential sensitivity of the developing rat brain to important environmental neurotoxicants. Developmental differences that may affect contaminant-induced changes in tissue DA concentrations include an age-dependent increase in dopamine transporters and reactive oxygen species protective mechanisms.

References:

1. Bemis, J.C. and Seegal, R.F. Polychlorinated biphenyls and methylmercury act synergistically to reduce rat brain dopamine content in vitro. Environ. Health Perspect. 107:879-885, 1999.

2. Bemis, J.C. and Seegal, R.F. Polychlorinated biphenyls and methylmercury alter intracellular calcium concentrations in rat cerebellar granule cells. Neurotoxicology 21:1123-1134, 2000.

Future Activities:

In the next year, we will (i) continue to determine the interactions between PCBs and MeHg on release and synthesis of dopamine and intracellular calcium concentrations using a mixture of Aroclors representative of the PCB patterns in fish from the Fox River and (ii) begin to determine the consequences of PCB and MeHg induced non-vesicularly stored dopamine on neuronal function. These experiments will allow us to investigate the differential sensitivity of tissue derived from developing versus adult brain and provide information on the mechanisms by which these contaminants, either alone or in combination, alter DA function. Furthermore, these studies will provide information necessary for experiments to be conducted in animals developmentally exposed to PCBs and MeHg.

Journal Articles:

No journal articles submitted with this report: View all 7 publications for this subproject

Supplemental Keywords:

mixtures, interactions., RFA, Scientific Discipline, Health, PHYSICAL ASPECTS, ENVIRONMENTAL MANAGEMENT, Toxicology, Health Risk Assessment, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Physical Processes, Children's Health, Molecular Biology/Genetics, genetic susceptability, Risk Assessment, developmental neurotoxicology, neurotoxic, sensitive populations, childhood cancer, biomarkers, PCBs, animal model, developmental effects, exposure, Human Health Risk Assessment, children, methylmercury, assessment of exposure, children's vulnerablity, residential populations, PCB, neurodevelopmental toxicity, neurobehavioral effects, biological markers, toxics

Progress and Final Reports:

Original Abstract

Final

Main Center Abstract and Reports:

R829390    CECEHDPR - University of Illinois FRIENDS Children’s Environmental Health Center

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R829390C001 Neurobehavioral Effects of PCBs and Methylmercury in Rats
R829390C002 Perinatal PCB Exposure and Neuropsychological/Auditory Function
R829390C003 FRIENDS Analytical Toxicology Core Facility
R829390C004 Developmental Effects of PCBs and Methylmercury