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Extramural Research

University of Illinois FRIENDS Children's Environmental Health Center

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FRIENDS

Center Director: Susan L. Schantz

Susan L Schantz
Susan L. Schantz

Project 1: Neurobehavioral Effects of PCBs and Methylmercury in Rats

Project 2: Perinatal PCBs and Neuropsychological/Auditory Function

Project 3: FRIENDS Analytical Toxicology Core Facility

Project 4: Developmental Effects of PCBs and Methylmercury


Overview

University of Illinois study area - Fox River, Green Bay, Wisconsin The FRIENDS Children's Environmental Health Center at the University of Illinois, Urbana-Champaign was funded by the U.S. EPA from 2001 to 2008. ("FRIENDS" is an acronym that stands for Fox River Environment and Diet Study.) The Center was a collaborative effort of investigators in epidemiology, toxicology, biostatistics, and developmental psychology from various institutions, including the University of Illinois at Urbana-Champaign, the University of Illinois at Chicago, Texas A&M University, the University of Oklahoma, the State University of New York at Buffalo, the New York State Department of Health, and Michigan State University.

A principal reason the Center was established was due to concerns about human exposure to neurotoxic chemicals present in fish in the Fox River and other rivers and lakes in northeastern Wisconsin. The goal was to investigate the neurodevelopmental effects of combined exposure to two common chemicals present in fish from this region, polychlorinated biphenyls (PCBs) and methylmercury (MeHg), in animal models and in humans exposed to these contaminants from fish. The epidemiological research within the Center focused on determining the fish consumption practices and exposure characteristics of Hmong refugees from countries such as Laos, Vietnam and Thailand living in northeastern Wisconsin, who practice subsistence fishing in the region. The laboratory animal studies used rodent models to assess the effects of early developmental exposure to PCBs and/or MeHg on cognitive and auditory function. The rodent studies employed an experimental mixture of PCBs (the Fox River PCB mix) that was created to mimic the PCB congener profile present in the fish consumed by the Hmong population in this region.

Environmental Exposures and Health Outcomes

Primary Environmental Exposures: Methylmercury (MeHg) and PCBs
Primary Health Outcomes: Neurodevelopment, neuropsychological and auditory function, neurobehavioral effects

Research Projects

Explaining exposure of contaminants found in fish to a mother.

Project 1: Neurobehavioral Effects of PCBs and Methylmercury in Rats
Animal studies were an extremely important component of the FRIENDS Center. In the lab, female rats were fed a mixture formulated to mimic actual human exposure to PCBs and MeHg from contaminated fish caught from the Fox River in Green Bay, Wisconsin. Exposure begins before pregnancy and continues through lactation until pups are weaned. In order to assess the effects of developmental PCB exposure, male and female offspring from each litter were tested on a battery of cognitive, motor, and auditory tests when they reach adulthood. The results were used by the Center's epidemiologists to guide the selection of outcome measures to be used in the children who are being followed in the community-based study. Brian Powers, a graduate student in the Schantz lab, observed auditory deficits in rats exposed to the Fox River PCB mixture during early development. In his study, two different tests of auditory function were employed: one assessed function of the peripheral sensory organ, the cochlea, and the other assessed central processing of auditory information as it travels from the cochlea through the brainstem. In other research conducted with the siblings of the rats that under went the hearing tests, Dr. Helen Sable, a research assistant professor in the Schantz lab, showed that rats exposed to the Fox River PCB mix during early development had problems with inhibitory control. When placed in an operant box with a lever to press, the rats had trouble "holding back" a response when one was not necessary or appropriate. Similar problems have been reported in PCB-exposed children and in children diagnosed with ADHD. In the future Dr. Sable hopes to investigate the effect of drugs used to treat ADHD on inhibitory control in PCB-exposed rats.

Project 2: Perinatal PCBs and Neuropsychological/Auditory Function
The primary research objectives of the community-based exposure project directed by Dr. Anne Sweeney were to understand the impact of prenatal exposure to contaminants found in fishmainly polychlorinated biphenyls (PCBs) and methylmercury (MeHg)on cognitive, motor, and auditory function in children. The centerpiece of this research was a prospective birth cohort study of Hmong and Lao women of reproductive age who live in Green Bay and Appleton, Wisconsin, and regularly eat fish caught in local PCB and MeHg-contaminated waters. Evidence suggests that infants exposed perinatally to PCBs or MeHg, or a combination of both, may be at risk for neurodevelopmental deficits. Investigators followed these infants from birth to about age 5, looking at other domains such as, working memory, attention, impulse control, motor balance, and very early verbal skills and knowledge, which could be affected by exposure to PCBs and other chemicals.

Project 3: FRIENDS Analytical Toxicology Core Facility
The objective of the Analytical Toxicology Core Facility (ATCF) is to provide analytical support to both the epidemiological and animal research projects of the FRIENDS Children's Environmental Health Center. The ATCF support involves the development of new analytical techniques, analyses of samples and analyses of data. All procedures are controlled by a strict QC/QA program. The techniques available Include GC with EC, FID, PID and Hall detection, HPLC with diode array, fluorescence and electrochemical detection, GC-MS, AAS, mercury determinations, high temperatures GPC for absolute molecular weight and molecular weight distribution determinations. This laboratory has extensive experience determining specific congeners of PCBs and pesticides and heavy metals at ppb levels in biological samples, and has participated in nationwide proficiency programs for PCBs, pesticides and mercury. The ATCF also performs a reporter gene bioassay for the quantification of total dioxin (TCDD) toxic equivalents (TEQs) in Hepa 1c1c7, mouse hepatoma cells, which are stably transfected with the reporter plasmid p2Dluc containing 2 copies of the DREDconsensus sequence.

Project 4: Developmental Effects of PCBs and Methylmercury
This laboratory-based project directed by Dr. Richard Seegal aided in understanding results obtained from the community based study by determining the mechanisms by which PCBs and methylmercury alter central nervous system function. Using a number of experimental models, including laboratory rodents and tissues from these animals, Dr. Seegal and his team investigated the effects of PCBs and MeHg, both individually and in combination, on neurotransmitter systems in the brain responsible for learning and behavior. The data that Dr. Seegal's group has collected shows that the effects of simultaneous exposure to these two neurotoxicants may be greater than the sum of the effects of exposure to the toxicants individually. Dr. Seegal also investigated the effects of PCBs and MeHg at different times during development. Using pinched off nerve endings, called synaptosomes, derived from animals of different ages and maintained in tissue culture, he has observed that a critical period exists early in development where animals are more susceptible to PCBs and MeHg. The turning point appears to be around the time of weaning, and this finding may have potential correlates with humans.In addition to these findings, Dr. Seegal has shown that methylmercury causes loss of cell viability, or cell death, through an oxidative stress-independent mechanism. Rather than methylmercury inducing oxidative stress leading to mitochondrial dysfunction, the oxidative stress appears to be further downstream, suggesting that treatment with antioxidants may not be very effective as a protective treatment for methylmercury exposure.

Publications

Publications: (2001-2008)

Centers Funded By:
Centers Funded by Epa and NIEHS

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