Superfund Research Program
PCB Effects on Uterine Muscle
Project Leader: Rita Loch-Caruso (University of Michigan)
Grant Number: P42ES004911
Funding Period: 1995 - 2006
Experiments during the last year have examined uterine tissue and cell responses to short-term exposures to PCB mixtures with different chlorine contents. It was found that PCB mixtures with lower chlorine contents were more potent stimulators of uterine contraction. In collaboration with other SBRP investigators, lower chlorinated products resulting from degradation of PCBs by bacteria isolated from the Hudson River were tested. These products were highly active in the uterus and the products of Aroclor 1254 and 1260 showed greatly increased effects on uterine contraction compared to the parent mixtures. Chemical analysis revealed that one of the most abundant products was 2,4,2',4'-tetrachlorobiphenyl which has previously been shown to stimulate uterine contractions. These data suggest that microbial dechlorination of PCBs may result in increased effects on uterine function.
Understanding the mechanisms by which PCBs stimulate uterine contractions was the aim of other research studies on the effects of Aroclor 1242 on rat uterine muscle cells. The results indicated that Aroclor 1242 increased intracellular calcium concentrations, apparently by activating voltage operated calcium channels on the cell membrane. In addition, they showed that Aroclor resulted in the release of arachidonic acid, but not inositol phosphate, from uterine cells by a calcium independent mechanism. Subsequent experiments showed that the arachidonic acid produced remained largely unchanged because the Aroclor 1242 inhibited its metabolism. Other studies showed that inhibitors of arachidonic acid release, but not inositol phosphate release, prevented Aroclor 1242-induced stimulation of uterine contractions. This suggests that the mechanism of action of Aroclor 1242 involves arachidonic acid-mediated release of intracellular calcium, possibly by activation of voltage operated calcium channels. Better understanding of the mechanism of action will provide information needed to improve the assessment of risk from PCB mixtures and their microbial degradation products.